TY  - CONF
AU  - Gašić, Vladimir
AU  - Pravdić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1899
AB  - Acute myeloid leukemia (AML) is a malignancy of hematopoetic tissue which occurs due to a halt in
differentiation, loss of proliferation control and dysregulated apoptosis of myeloid progenitor cells. In
many cancers, as well as AML, dysregulation of apoptosis constitutes the basis of pathogenesis and this
phenomenon is important for chemotherapy success. Pharmacotranscriptomic markers of AML
prognosis could be targets of specific therapy. The anti-apoptotic gene BCL2 (B-cell lymphoma protein
2), the pro-apoptotic BAX (BCL2-associated X) and genes involved in drug resistance, like MDR1
could have a significant impact on AML prognosis and therapy response. Bone-marrow samples at
diagnosis were collected from 51 adult patients with AML-NK. Expressions of BCL2, BAX and MDR1
were analysed using the real-time polymerase chain reaction method. Statistical evaluation was
performed. The presence of chemoresistance was found to be associated with overexpression of BCL2
(BCL2+) (p=0.018), while underexpression of BAX in patients has shown a greater affinity towards
relapse (p=0.034). Evaluating the expressions of BCL2 and BAX in a combined effect has shown that
87% of patients with BAX/BCL2low status were resistant to therapy (p=0.024). BCL2+ status was
associated with high expression of MDR1 (p<0.001). Likewise, high expression of MDR1 was
associated with the absence of NPM1 and FLT3-ITD mutations (p=0.048 and p=0.010, respectively).
This is the first study that focused only on AML-NK patients, when it comes to analysis of BCL2, BAX
and MDR1 gene expression profiles. The results of this preliminary study have shown that high BCL2
expression would likely lead to resistance from chemotherapy, making anti-BCL2 treatment a viable
option in patients with this expression profile. A study on a larger group of patients could clarify the
prognostic importance of the studied genes in adult AML-NK patients and improve the precision
medicine approach in the field of hematology.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia
VL  - 7
VL  - 2 (Special edition)
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1899
ER  - 

@conference{
author = "Gašić, Vladimir and Pravdić, Zlatko and Suvajdžić Vuković, Nada and Marjanović, Irena and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Acute myeloid leukemia (AML) is a malignancy of hematopoetic tissue which occurs due to a halt in
differentiation, loss of proliferation control and dysregulated apoptosis of myeloid progenitor cells. In
many cancers, as well as AML, dysregulation of apoptosis constitutes the basis of pathogenesis and this
phenomenon is important for chemotherapy success. Pharmacotranscriptomic markers of AML
prognosis could be targets of specific therapy. The anti-apoptotic gene BCL2 (B-cell lymphoma protein
2), the pro-apoptotic BAX (BCL2-associated X) and genes involved in drug resistance, like MDR1
could have a significant impact on AML prognosis and therapy response. Bone-marrow samples at
diagnosis were collected from 51 adult patients with AML-NK. Expressions of BCL2, BAX and MDR1
were analysed using the real-time polymerase chain reaction method. Statistical evaluation was
performed. The presence of chemoresistance was found to be associated with overexpression of BCL2
(BCL2+) (p=0.018), while underexpression of BAX in patients has shown a greater affinity towards
relapse (p=0.034). Evaluating the expressions of BCL2 and BAX in a combined effect has shown that
87% of patients with BAX/BCL2low status were resistant to therapy (p=0.024). BCL2+ status was
associated with high expression of MDR1 (p<0.001). Likewise, high expression of MDR1 was
associated with the absence of NPM1 and FLT3-ITD mutations (p=0.048 and p=0.010, respectively).
This is the first study that focused only on AML-NK patients, when it comes to analysis of BCL2, BAX
and MDR1 gene expression profiles. The results of this preliminary study have shown that high BCL2
expression would likely lead to resistance from chemotherapy, making anti-BCL2 treatment a viable
option in patients with this expression profile. A study on a larger group of patients could clarify the
prognostic importance of the studied genes in adult AML-NK patients and improve the precision
medicine approach in the field of hematology.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia",
volume = "7, 2 (Special edition)",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1899"
}

Gašić, V., Pravdić, Z., Suvajdžić Vuković, N., Marjanović, I., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7.
https://hdl.handle.net/21.15107/rcub_imagine_1899

Gašić V, Pravdić Z, Suvajdžić Vuković N, Marjanović I, Karan-Đurašević T, Pavlović S, Tošić N. Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia. in Genetics & Applications. 2023;7.
https://hdl.handle.net/21.15107/rcub_imagine_1899 .

Gašić, Vladimir, Pravdić, Zlatko, Suvajdžić Vuković, Nada, Marjanović, Irena, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia" in Genetics & Applications, 7 (2023),
https://hdl.handle.net/21.15107/rcub_imagine_1899 .

TY  - CONF
AU  - Zečević, Marko
AU  - Kotur, Nikola
AU  - Ristivojević, Bojan
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2029
AB  - Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity,
currently is the focus of multiple genome-wide association studies (GWAS) in populations
affected by the pandemic. This is the first study from Serbia that performed a GWAS of
COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128
hospitalized COVID-19 patients from the Serbian population was enrolled in the study.
We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients
without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients,
using a genotyping array followed by imputation of missing genotypes. We have detected
a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with
a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated
a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L
and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and
severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19
pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6,MRPL36, p
= 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1,LURAP1L, p = 8.69 ×
10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and
have been previously associated with respiratory diseases such as asthma and COVID-19
or reported as differentially expressed in COVID-19 gene expression profiling studies.
Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which
could contribute to a better understanding of the COVID-19 host genetics in different
populations.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - Genome-wide association analysis for severe COVID-19 in Serbian population
EP  - 84
SP  - 84
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2029
ER  - 

@conference{
author = "Zečević, Marko and Kotur, Nikola and Ristivojević, Bojan and Gašić, Vladimir and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2023",
abstract = "Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity,
currently is the focus of multiple genome-wide association studies (GWAS) in populations
affected by the pandemic. This is the first study from Serbia that performed a GWAS of
COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128
hospitalized COVID-19 patients from the Serbian population was enrolled in the study.
We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients
without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients,
using a genotyping array followed by imputation of missing genotypes. We have detected
a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with
a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated
a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L
and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and
severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19
pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6,MRPL36, p
= 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1,LURAP1L, p = 8.69 ×
10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and
have been previously associated with respiratory diseases such as asthma and COVID-19
or reported as differentially expressed in COVID-19 gene expression profiling studies.
Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which
could contribute to a better understanding of the COVID-19 host genetics in different
populations.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "Genome-wide association analysis for severe COVID-19 in Serbian population",
pages = "84-84",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2029"
}

Zečević, M., Kotur, N., Ristivojević, B., Gašić, V., Zukić, B., Pavlović, S.,& Stanković, B.. (2023). Genome-wide association analysis for severe COVID-19 in Serbian population. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 84-84.
https://hdl.handle.net/21.15107/rcub_imagine_2029

Zečević M, Kotur N, Ristivojević B, Gašić V, Zukić B, Pavlović S, Stanković B. Genome-wide association analysis for severe COVID-19 in Serbian population. in 4th Belgrade Bioinformatics Conference. 2023;4:84-84.
https://hdl.handle.net/21.15107/rcub_imagine_2029 .

Zečević, Marko, Kotur, Nikola, Ristivojević, Bojan, Gašić, Vladimir, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Genome-wide association analysis for severe COVID-19 in Serbian population" in 4th Belgrade Bioinformatics Conference, 4 (2023):84-84,
https://hdl.handle.net/21.15107/rcub_imagine_2029 .

TY  - CONF
AU  - Đorđe, Pavlović
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2127
AB  - Introduction: Acute myeloid leukemia (AML) is a heterogeneous malignant disease, that accounts for
80% of all acute leukemias in adults. Imprecise risk stratification and lack of personalized treatment creates a constant need to find new prognostic markers and targets for innovative therapeutics. Recently,
thissearch has pointed towards non-coding RNAs(ncRNA). Numerousstudies have shown dysregulation
of lncRNA GAS5 in cancers, but it was poorly investigated in AML. Since GAS5 actslike a molecularsponge
for miR-222, co-expression profiles of these non-coding RNAs could be novel prognostic markersin AML.
Methods: GAS5 expression levels were analysed in 94 AML patients and 14 healthy controls using RealTime PCR and miR-222 expression levels were analysed in a subgroup of 39 patients with normal karyotype (AML-NK). ROC curve analyses were used to find a cut-off value between GAS5high and GAS5low,
while the median value was used for distinguishing between miR-222high and miR-222low.
Results: We showed that GAS5 expression in AML patients was lower compared to healthy controls.
Lower GAS5 expression on diagnosis was related to an adverse prognosis. The disease-free survival and
the overallsurvival were lower in the GAS5low group butsurvival analysisfailed to confirm thisfinding. In
the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic
effect of GAS5low/miR-222high status on disease prognosis was not established.
Conclusion:Our findingsindicate the potential prognostic significance of GAS5 expression and the need
for further investigation of these two non-coding RNAs and their potential roles in leukemogenesis.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients
EP  - 72
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2127
ER  - 

@conference{
author = "Đorđe, Pavlović and Tošić, Nataša and Zukić, Branka and Pravić, Zlatko and Suvajdžić Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2023",
abstract = "Introduction: Acute myeloid leukemia (AML) is a heterogeneous malignant disease, that accounts for
80% of all acute leukemias in adults. Imprecise risk stratification and lack of personalized treatment creates a constant need to find new prognostic markers and targets for innovative therapeutics. Recently,
thissearch has pointed towards non-coding RNAs(ncRNA). Numerousstudies have shown dysregulation
of lncRNA GAS5 in cancers, but it was poorly investigated in AML. Since GAS5 actslike a molecularsponge
for miR-222, co-expression profiles of these non-coding RNAs could be novel prognostic markersin AML.
Methods: GAS5 expression levels were analysed in 94 AML patients and 14 healthy controls using RealTime PCR and miR-222 expression levels were analysed in a subgroup of 39 patients with normal karyotype (AML-NK). ROC curve analyses were used to find a cut-off value between GAS5high and GAS5low,
while the median value was used for distinguishing between miR-222high and miR-222low.
Results: We showed that GAS5 expression in AML patients was lower compared to healthy controls.
Lower GAS5 expression on diagnosis was related to an adverse prognosis. The disease-free survival and
the overallsurvival were lower in the GAS5low group butsurvival analysisfailed to confirm thisfinding. In
the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic
effect of GAS5low/miR-222high status on disease prognosis was not established.
Conclusion:Our findingsindicate the potential prognostic significance of GAS5 expression and the need
for further investigation of these two non-coding RNAs and their potential roles in leukemogenesis.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients",
pages = "72-72",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2127"
}

Đorđe, P., Tošić, N., Zukić, B., Pravić, Z., Suvajdžić Vuković, N., Pavlović, S.,& Gašić, V.. (2023). Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 72-72.
https://hdl.handle.net/21.15107/rcub_imagine_2127

Đorđe P, Tošić N, Zukić B, Pravić Z, Suvajdžić Vuković N, Pavlović S, Gašić V. Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:72-72.
https://hdl.handle.net/21.15107/rcub_imagine_2127 .

Đorđe, Pavlović, Tošić, Nataša, Zukić, Branka, Pravić, Zlatko, Suvajdžić Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Expression profiles of long non-coding RNA gas5 and microrna-222 in younger AML patients" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):72-72,
https://hdl.handle.net/21.15107/rcub_imagine_2127 .

TY  - CONF
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Tošić, Nataša
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Milošević, Goran
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2128
AB  - Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia
EP  - 81
SP  - 81
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2128
ER  - 

@conference{
author = "Ristivojević, Bojan and Kotur, Nikola and Tošić, Nataša and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Milošević, Goran and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Introduction: The NUDT15 is new pharmacogene of importance for 6-mercaptopurine therapy, given to
children with acute lymphoblastic leukemia (ALL). The association ofside effectsin children with variants
in NUDT15 are well established in Asian populations, yet the relevance ofthis pharmacogene in European
populationsremainslargely unexplored. The aim of thisstudy wasto identify pharmacogenetic variants
in coding and neighbouring regions of NUDT15 gene and analyse if the expression levels of NUDT15 can
predict the occurence of side effects of 6-mercaptopurine during the maintenance therapy in children
with ALL of Serbian origin.
Methods: The genotyping of coding and neighbouring regions of NUDT15 gene was performed using
PCR and Sangersequencing based technology in 48 children with ALL. NUDT15 expression was analyzed
in mononuclear cells of 24 ALL patients at diagnosis and 6 healthy controls by qRT-PCR, and association
with surogate markers was assessed using adequate statistical methodology.
Results: The genotypig revealed the presence of 5 variantsin NUDT15 (NUDT15(NM_018283.4):c.36A>C,
NUDT15(NM_018283.4):c.158+117C>T,NUDT15(NM_018283.4):c.158+174G>A,NUDT15(NM_018283.4):c.159-
91G>A,NUDT15(NM_018283.4):c.*7G>A), none of them with effects on the expression or the function of
NUDT15 protein. There was no statistically significant association between the expression of NUDT15 at
diagnosis and the surogate markers of side effects (number of episodes of leukopenia (p=0.821), number of weeks without therapy (p=0.507), number of weeks with lower dose (p=0.434), average doses
(p=0.374)) of 6-mercaptopurine during the maintenance therapy.
Conclusion: Presently, NUDT15 cannot be used as a pharmacogene in predicting the toxicity of 6-mercaptopurine terapy in children with ALL in Serbia.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia",
pages = "81-81",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2128"
}

Ristivojević, B., Kotur, N., Tošić, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Milošević, G., Pavlović, S.,& Zukić, B.. (2023). NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128

Ristivojević B, Kotur N, Tošić N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Milošević G, Pavlović S, Zukić B. NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:81-81.
https://hdl.handle.net/21.15107/rcub_imagine_2128 .

Ristivojević, Bojan, Kotur, Nikola, Tošić, Nataša, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Milošević, Goran, Pavlović, Sonja, Zukić, Branka, "NUDT15 as potential marker for pharmacogenetic-guided 6-mercaptopurine therapy in children with acute lymphoblastic leukemia in Serbia" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):81-81,
https://hdl.handle.net/21.15107/rcub_imagine_2128 .

TY  - CONF
AU  - Gašić, Vladimir
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Perić, Jelena
AU  - Ristivojević, Bojan
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://belbi.bg.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2040
AB  - Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side
effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due
to treatment. More efficient treatment of pediatric ALL has been developed by avoiding
drug adverse effects included in the treatment protocols. Therefore, implementation of
pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing
(NGS) contributed to discovery of novel genetic markers, potential candidates for targeted
therapy and predictors of efficacy and toxicity of drugs.
We aimed to discover novel potential pharmacogenomic markers in pediatric ALL.
DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using
the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48
oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne
(Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC
response markers was designed. Predicting the effects of novel variants was performed
using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability
and modeling we used STRUM method and i-TASSER server.
In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been
identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T
possess potential as pharmacogenomic markers, therefore, they are candidates for
molecular targeted therapy. In the exome sequencing study, according to the prediction
algorithms, 3 new potential markers in pharmacogenes related to GC response have been
identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812.
Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations,
candidates for targeted molecular therapy, as well as 3 novel germinative variants,
potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic
profiling of each pediatric ALL patient is indispensable for new therapy approaches and it
could lead to better outcomes.
PB  - Belgrade : Institute of molecular genetics and genetic engineering
C3  - 4th Belgrade Bioinformatics Conference
T1  - In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment
EP  - 95
SP  - 95
VL  - 4
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2040
ER  - 

@conference{
author = "Gašić, Vladimir and Kotur, Nikola and Stanković, Biljana and Pavlović, Đorđe and Jelovac, Marina and Perić, Jelena and Ristivojević, Bojan and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Acute lymphoblastic leukemia (ALL) is the most common childhood neoplasm. Side
effects of therapy occur in 75% of patients and 1-3% of patients have a lethal outcome due
to treatment. More efficient treatment of pediatric ALL has been developed by avoiding
drug adverse effects included in the treatment protocols. Therefore, implementation of
pharmacogenomics is paramount in pediatric ALL treatment. Next generation sequencing
(NGS) contributed to discovery of novel genetic markers, potential candidates for targeted
therapy and predictors of efficacy and toxicity of drugs.
We aimed to discover novel potential pharmacogenomic markers in pediatric ALL.
DNA samples from bone marrow of 17 pediatric ALL patients were analyzed using
the platform TruSeq Amplicon – Cancer Panel (Ilumina) for somatic mutations in 48
oncogenes. DNA samples from blood of 100 individuals, using the platform TruSightOne
(Ilumina), were analyzed for germinative mutations. An in-house virtual panel for GC
response markers was designed. Predicting the effects of novel variants was performed
using the SIFT, PolyPhen-2 and PROVEAN software tools. For protein structure stability
and modeling we used STRUM method and i-TASSER server.
In the NGS study of somatic mutations in pediatric ALL, 9 novel variants have been
identified. Bioinformatic analysis has shown that STK11 c.1023G>T and ERBB2 c.2341C>T
possess potential as pharmacogenomic markers, therefore, they are candidates for
molecular targeted therapy. In the exome sequencing study, according to the prediction
algorithms, 3 new potential markers in pharmacogenes related to GC response have been
identified, ABCB1 c.947A>G, NCOA3 rs138733364 and TBX21 rs14059812.
Using NGS analysis and prediction algorithms, we have detected 2 novel somatic mutations,
candidates for targeted molecular therapy, as well as 3 novel germinative variants,
potential pharmacogenomic markers of GC response in pediatric ALL. Pharmacogenomic
profiling of each pediatric ALL patient is indispensable for new therapy approaches and it
could lead to better outcomes.",
publisher = "Belgrade : Institute of molecular genetics and genetic engineering",
journal = "4th Belgrade Bioinformatics Conference",
title = "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment",
pages = "95-95",
volume = "4",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2040"
}

Gašić, V., Kotur, N., Stanković, B., Pavlović, Đ., Jelovac, M., Perić, J., Ristivojević, B., Pavlović, S.,& Zukić, B.. (2023). In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference
Belgrade : Institute of molecular genetics and genetic engineering., 4, 95-95.
https://hdl.handle.net/21.15107/rcub_imagine_2040

Gašić V, Kotur N, Stanković B, Pavlović Đ, Jelovac M, Perić J, Ristivojević B, Pavlović S, Zukić B. In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment. in 4th Belgrade Bioinformatics Conference. 2023;4:95-95.
https://hdl.handle.net/21.15107/rcub_imagine_2040 .

Gašić, Vladimir, Kotur, Nikola, Stanković, Biljana, Pavlović, Đorđe, Jelovac, Marina, Perić, Jelena, Ristivojević, Bojan, Pavlović, Sonja, Zukić, Branka, "In Silico analysis and prediction of novel pharmacogenomic markers of pediatric ALL treatment" in 4th Belgrade Bioinformatics Conference, 4 (2023):95-95,
https://hdl.handle.net/21.15107/rcub_imagine_2040 .

TY  - JOUR
AU  - Pravdić, Zlatko
AU  - Vuković, Nada Suvajdžić
AU  - Gašić, Vladimir
AU  - Marjanović, Irena
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2023
UR  - https://sciendo.com/article/10.2478/raon-2023-0017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2291
AB  - Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p < 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely
PB  - Sciendo
T2  - Radiology and Oncology
T1  - The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients
EP  - 248
IS  - 2
SP  - 239
VL  - 57
DO  - 10.2478/raon-2023-0017
ER  - 

@article{
author = "Pravdić, Zlatko and Vuković, Nada Suvajdžić and Gašić, Vladimir and Marjanović, Irena and Karan-Đurašević, Teodora and Pavlović, Sonja and Tošić, Nataša",
year = "2023",
abstract = "Background: Deregulation of the apoptotic process underlies the pathogenesis of many cancers, including leukemia, but is also very important for the success of chemotherapy treatment. Therefore, the gene expression profile of main apoptotic factors, such as anti-apoptotic BCL2 (B-cell lymphoma protein 2) and pro-apoptotic BAX (BCL2-associated X), as well as genes involved in the multi-drug resistance (ABCB1), could have significant impact on the prognosis and could be used as targets for specific therapy.Patients and methodsWe analyzed the expression of BCL2, BAX, and ABCB1 in bone-marrow samples collected at diagnosis from 51 adult patients with acute myeloid leukemia with normal karyotype (AML-NK) using real-time polymerase chain reaction method, and examined their prognostic potential.ResultsIncreased expression of BCL2 (BCL2+) was associated with the presence of chemoresistance (p = 0.024), while patients with low BAX expression were more prone to relapse (p = 0.047). Analysis of the combined effect of BCL2 and BAX expression showed that 87% of patients with BAX/BCL2low status were resistant to therapy (p = 0.044). High expression of ABCB1 was associated with BCL2+ status (p < 0.001), and with absence FLT3-ITD mutations (p = 0.019).ConclusionsThe present analysis of BCL2, BAX, and ABCB1 gene expression profiles is the first study focusing solely",
publisher = "Sciendo",
journal = "Radiology and Oncology",
title = "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients",
pages = "248-239",
number = "2",
volume = "57",
doi = "10.2478/raon-2023-0017"
}

Pravdić, Z., Vuković, N. S., Gašić, V., Marjanović, I., Karan-Đurašević, T., Pavlović, S.,& Tošić, N.. (2023). The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology
Sciendo., 57(2), 239-248.
https://doi.org/10.2478/raon-2023-0017

Pravdić Z, Vuković NS, Gašić V, Marjanović I, Karan-Đurašević T, Pavlović S, Tošić N. The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients. in Radiology and Oncology. 2023;57(2):239-248.
doi:10.2478/raon-2023-0017 .

Pravdić, Zlatko, Vuković, Nada Suvajdžić, Gašić, Vladimir, Marjanović, Irena, Karan-Đurašević, Teodora, Pavlović, Sonja, Tošić, Nataša, "The influence of BCL2, BAX, and ABCB1 gene expression on prognosis of adult de novo acute myeloid leukemia with normal karyotype patients" in Radiology and Oncology, 57, no. 2 (2023):239-248,
https://doi.org/10.2478/raon-2023-0017 . .

TY  - CONF
AU  - Kotur, Nikola
AU  - Skakić, Anita
AU  - Klaassen, Kristel
AU  - Gašić, Vladimir
AU  - Jelovac, Marina
AU  - Ristivojević, Bojan
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1904
AB  - COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The
emerging amount of data indicates that vitamin D could be important for clinical presentation of
COVID-19. Here, we investigated association of genetic variants related to the altered level and
bioavailability of vitamin D with clinical severity of COVID-19. We analyzed variants in genes
significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, and CYP2R1
rs10741657), and vitamin D effect (VDR rs2228570) in 120 Serbian adult and pediatric COVID-19
patients using allelic discrimination. Furthermore, we carried out comparative population genetic
analysis among European and other worldwide populations to investigate variation in allelic
frequencies of selected variants. The results showed that DHCR7/NADSYN rs12785878 and CYP2R1
rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017,
respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the
odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There
were no associations between selected genetic variants and disease severity in pediatric patients.
Comparative population genetic analysis revealed that Serbian population had the lowest frequency of
CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and
0.66 in Spanish and Italian population, respectively), suggesting that other populations should also
investigate the relationship of CYP2R1 variant and the COVID-19 disease course. The results of the
study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults.
This could direct prevention strategies based on population specific nutrigenetic profiles.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - Covid-19 disease severity associated with vitamin d related genetic Variants
IS  - 2 (Special edition
SP  - 144
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1904
ER  - 

@conference{
author = "Kotur, Nikola and Skakić, Anita and Klaassen, Kristel and Gašić, Vladimir and Jelovac, Marina and Ristivojević, Bojan and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2023",
abstract = "COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The
emerging amount of data indicates that vitamin D could be important for clinical presentation of
COVID-19. Here, we investigated association of genetic variants related to the altered level and
bioavailability of vitamin D with clinical severity of COVID-19. We analyzed variants in genes
significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, and CYP2R1
rs10741657), and vitamin D effect (VDR rs2228570) in 120 Serbian adult and pediatric COVID-19
patients using allelic discrimination. Furthermore, we carried out comparative population genetic
analysis among European and other worldwide populations to investigate variation in allelic
frequencies of selected variants. The results showed that DHCR7/NADSYN rs12785878 and CYP2R1
rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017,
respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the
odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There
were no associations between selected genetic variants and disease severity in pediatric patients.
Comparative population genetic analysis revealed that Serbian population had the lowest frequency of
CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and
0.66 in Spanish and Italian population, respectively), suggesting that other populations should also
investigate the relationship of CYP2R1 variant and the COVID-19 disease course. The results of the
study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults.
This could direct prevention strategies based on population specific nutrigenetic profiles.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "Covid-19 disease severity associated with vitamin d related genetic Variants",
number = "2 (Special edition",
pages = "144",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1904"
}

Kotur, N., Skakić, A., Klaassen, K., Gašić, V., Jelovac, M., Ristivojević, B., Zukić, B., Pavlović, S.,& Stanković, B.. (2023). Covid-19 disease severity associated with vitamin d related genetic Variants. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition), 144.
https://hdl.handle.net/21.15107/rcub_imagine_1904

Kotur N, Skakić A, Klaassen K, Gašić V, Jelovac M, Ristivojević B, Zukić B, Pavlović S, Stanković B. Covid-19 disease severity associated with vitamin d related genetic Variants. in Genetics & Applications. 2023;7(2 (Special edition):144.
https://hdl.handle.net/21.15107/rcub_imagine_1904 .

Kotur, Nikola, Skakić, Anita, Klaassen, Kristel, Gašić, Vladimir, Jelovac, Marina, Ristivojević, Bojan, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Covid-19 disease severity associated with vitamin d related genetic Variants" in Genetics & Applications, 7, no. 2 (Special edition (2023):144,
https://hdl.handle.net/21.15107/rcub_imagine_1904 .

TY  - CONF
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Jelovac, Marina
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1902
AB  - Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute
lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase,
inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal
transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was
to determine if the selected genetic variants are associated with the development of VIPN in ALL
children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic
markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect
variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117
(rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their
association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17
pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency
distribution for European population were extracted from public databases. During the treatment,
17.86% of patients developed VIPN. Association analyses have shown that none of the investigated
genetic variants contributed to the occurrence of VIPN in our study group. Population
pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN.
Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More
comprehensive approaches are needed to identify panel of genes that could explain the VIPN
development after VCR administration in ALL patients. Utilizing better designed GWAS studies and
more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive
tests of VIPN to individualize therapy for ALL in children.
PB  - Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
C3  - Genetics & Applications
T1  - The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia
IS  - 2 (Special edition)
SP  - 109
VL  - 7
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1902
ER  - 

@conference{
author = "Ristivojević, Bojan and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Pavlović, Đorđe and Jelovac, Marina and Pavlović, Sonja and Zukić, Branka",
year = "2023",
abstract = "Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute
lymphoblastic leukemia (ALL). By destabilization of microtubules, VCR arrests cells in metaphase,
inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal
transport, which leads to vincristine-induced peripheral neuropathy (VIPN). The aim of this study was
to determine if the selected genetic variants are associated with the development of VIPN in ALL
children treated with VCR in Serbia. This study also aimed to discover candidate pharmacogenomic
markers of VIPN in Serbian population. PCR and sequencing-based methodology was used to detect
variants in following genes: CYP3А5 (rs776746), CEP72 (rs924607), ACTG1 (rs1135989), MIR3117
(rs12402181) and MIR4481 (rs7896283). Statistical analyses were performed for investigation of their
association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17
pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency
distribution for European population were extracted from public databases. During the treatment,
17.86% of patients developed VIPN. Association analyses have shown that none of the investigated
genetic variants contributed to the occurrence of VIPN in our study group. Population
pharmacogenomics study didn’t reveal valid candidate pharmacovariants for the occurrence of VIPN.
Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable. More
comprehensive approaches are needed to identify panel of genes that could explain the VIPN
development after VCR administration in ALL patients. Utilizing better designed GWAS studies and
more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive
tests of VIPN to individualize therapy for ALL in children.",
publisher = "Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo",
journal = "Genetics & Applications",
title = "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia",
number = "2 (Special edition)",
pages = "109",
volume = "7",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1902"
}

Ristivojević, B., Kotur, N., Stanković, B., Gašić, V., Pavlović, Đ., Jelovac, M., Pavlović, S.,& Zukić, B.. (2023). The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications
Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo., 7(2 (Special edition)), 109.
https://hdl.handle.net/21.15107/rcub_imagine_1902

Ristivojević B, Kotur N, Stanković B, Gašić V, Pavlović Đ, Jelovac M, Pavlović S, Zukić B. The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia. in Genetics & Applications. 2023;7(2 (Special edition)):109.
https://hdl.handle.net/21.15107/rcub_imagine_1902 .

Ristivojević, Bojan, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Pavlović, Đorđe, Jelovac, Marina, Pavlović, Sonja, Zukić, Branka, "The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia" in Genetics & Applications, 7, no. 2 (Special edition) (2023):109,
https://hdl.handle.net/21.15107/rcub_imagine_1902 .

TY  - CONF
AU  - Pavlović, Đorđe
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravdić, Zlatko
AU  - Suvajdžić Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1742
AB  - Akutna mijeloidna leukemija (AML) je heterogeno maligno oboljenje kako na
kliničkom tako i na genetičkom nivou. AML ima lošu prognozu, i zato postoji
konstantna potreba za novim prognostičkim markerima, kao i markerima koji
mogu biti mete za inovativne terapeutike. U skorije vreme potraga za novim
biomarkerima je naučnicima skrenula pažnju ka nekodirajućim RNK, naročito
dugim nekodirajućim RNK (dnkRNK) i mikroRNK (miRNK). U ovom radu ispitali
smo nivo ekspresije „growth arrest-specific transcript 5“ (GAS5) dnkRNK kod 94
mlađih osoba obolelih od AML, kao i nivo ekspresije miR-222 u grupi od 39
osoba obolelih od AML sa normalnim kariotipom (AML-NK), u cilju da
ispitamo njihov prognostički potencijal. Naši rezultati su pokazali da je nivo
ekspresije GAS5 kod obolelih od AML niži u poređenju sa zdravim kontrolama, i
češći je u grupi sa nepovoljnom prognozom. U AML-NK grupi pacijenti su imali
povišenu ekspresiju miR-222 u poređenju sa zdravim kontrolama. Sinergistički
efekat „GAS5low/miR-222 high“ nije utvrđen. Ovo je prva studija koja je ispitala
interakciju ekspresije GAS5 i miR-222 kod obolelih od AML. Naši rezultati
indikuju potrebu za daljim ispitivanjem ove dve nekodirajuće RNK i njihove
potencijalne uloge u leukemogenezi i prognostici AML pacijenata.
AB  - Акутна мијелоидна леукемија (АМЛ) је хетерогено малигно обољење како на
клиничком тако и на генетичком нивоу. АМЛ има лошу прогнозу, и зато постоји
константна потреба за новим прогностичким маркерима, као и маркерима који
могу бити мете за иновативне терапеутике. У скорије време потрага за новим
биомаркерима је научницима скренула пажњу ка некодирајућим РНК, нарочито
дугим некодирајућим РНК (днкРНК) и микроРНК (миРНК). У овом раду испитали
смо ниво експресије „growth arrest-specific transcript 5“ (GAS5) днкРНК код 94
млађих особа оболелих од АМЛ, као и ниво експресије miR-222 у групи од 39
особа оболелих од АМЛ са нормалним кариотипом (АМЛ-НК), у циљу да
испитамо њихов прогностички потенцијал. Наши резултати су показали да је ниво
експресије GAS5 код оболелих од АМЛ нижи у поређењу са здравим контролама, и
чешћи је у групи са неповољном прогнозом. У АМЛ-НК групи пацијенти су имали
повишену експресију miR-222 у поређењу са здравим контролама. Синергистички
ефекат „GAS5low/miR-222 high“ није утврђен. Ово је прва студија која је испитала
интеракцију експресије GAS5 и miR-222 код оболелих од АМЛ. Наши резултати
индикују потребу за даљим испитивањем ове две некодирајуће РНК и њихове
потенцијалне улоге у леукемогенези и прогностици АМЛ пацијената.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML
T1  - Експресиони образац дуге некодирајуће РНК GAS5 и микроРНК- 222 код млађих пацијената оболелих од АМЛ
SP  - 302
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1742
ER  - 

@conference{
author = "Pavlović, Đorđe and Tošić, Nataša and Zukić, Branka and Pravdić, Zlatko and Suvajdžić Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2022",
abstract = "Akutna mijeloidna leukemija (AML) je heterogeno maligno oboljenje kako na
kliničkom tako i na genetičkom nivou. AML ima lošu prognozu, i zato postoji
konstantna potreba za novim prognostičkim markerima, kao i markerima koji
mogu biti mete za inovativne terapeutike. U skorije vreme potraga za novim
biomarkerima je naučnicima skrenula pažnju ka nekodirajućim RNK, naročito
dugim nekodirajućim RNK (dnkRNK) i mikroRNK (miRNK). U ovom radu ispitali
smo nivo ekspresije „growth arrest-specific transcript 5“ (GAS5) dnkRNK kod 94
mlađih osoba obolelih od AML, kao i nivo ekspresije miR-222 u grupi od 39
osoba obolelih od AML sa normalnim kariotipom (AML-NK), u cilju da
ispitamo njihov prognostički potencijal. Naši rezultati su pokazali da je nivo
ekspresije GAS5 kod obolelih od AML niži u poređenju sa zdravim kontrolama, i
češći je u grupi sa nepovoljnom prognozom. U AML-NK grupi pacijenti su imali
povišenu ekspresiju miR-222 u poređenju sa zdravim kontrolama. Sinergistički
efekat „GAS5low/miR-222 high“ nije utvrđen. Ovo je prva studija koja je ispitala
interakciju ekspresije GAS5 i miR-222 kod obolelih od AML. Naši rezultati
indikuju potrebu za daljim ispitivanjem ove dve nekodirajuće RNK i njihove
potencijalne uloge u leukemogenezi i prognostici AML pacijenata., Акутна мијелоидна леукемија (АМЛ) је хетерогено малигно обољење како на
клиничком тако и на генетичком нивоу. АМЛ има лошу прогнозу, и зато постоји
константна потреба за новим прогностичким маркерима, као и маркерима који
могу бити мете за иновативне терапеутике. У скорије време потрага за новим
биомаркерима је научницима скренула пажњу ка некодирајућим РНК, нарочито
дугим некодирајућим РНК (днкРНК) и микроРНК (миРНК). У овом раду испитали
смо ниво експресије „growth arrest-specific transcript 5“ (GAS5) днкРНК код 94
млађих особа оболелих од АМЛ, као и ниво експресије miR-222 у групи од 39
особа оболелих од АМЛ са нормалним кариотипом (АМЛ-НК), у циљу да
испитамо њихов прогностички потенцијал. Наши резултати су показали да је ниво
експресије GAS5 код оболелих од АМЛ нижи у поређењу са здравим контролама, и
чешћи је у групи са неповољном прогнозом. У АМЛ-НК групи пацијенти су имали
повишену експресију miR-222 у поређењу са здравим контролама. Синергистички
ефекат „GAS5low/miR-222 high“ није утврђен. Ово је прва студија која је испитала
интеракцију експресије GAS5 и miR-222 код оболелих од АМЛ. Наши резултати
индикују потребу за даљим испитивањем ове две некодирајуће РНК и њихове
потенцијалне улоге у леукемогенези и прогностици АМЛ пацијената.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML, Експресиони образац дуге некодирајуће РНК GAS5 и микроРНК- 222 код млађих пацијената оболелих од АМЛ",
pages = "302",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1742"
}

Pavlović, Đ., Tošić, N., Zukić, B., Pravdić, Z., Suvajdžić Vuković, N., Pavlović, S.,& Gašić, V.. (2022). Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 302.
https://hdl.handle.net/21.15107/rcub_imagine_1742

Pavlović Đ, Tošić N, Zukić B, Pravdić Z, Suvajdžić Vuković N, Pavlović S, Gašić V. Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML. in Treći kongres biologa Srbije. 2022;:302.
https://hdl.handle.net/21.15107/rcub_imagine_1742 .

Pavlović, Đorđe, Tošić, Nataša, Zukić, Branka, Pravdić, Zlatko, Suvajdžić Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Ekspresioni obrazac duge nekodirajuće RNK GAS5 i mikroRNK- 222 kod mlađih pacijenata obolelih od AML" in Treći kongres biologa Srbije (2022):302,
https://hdl.handle.net/21.15107/rcub_imagine_1742 .

TY  - JOUR
AU  - Ristivojević, Bojan
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Lazić, Jelena
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1569
AB  - Uvod/Cilj Vinkristin je jedan od ključnih lekova u protokolima lečenja dečje akutne limfoblastne leukemije (ALL). Vinkristin dovodi do destabilizacije mikrotubula, čime se ćelija zaustavlja u metafazi i indukuje apoptoza. Takođe dovodi do degradacije aksona i poremećaja aksonskog transporta, uzrokujući vinkristinom indukovanu perifernu neuropatiju (VIPN). Cilj ove studije bio je da istraži povezanost pet varijanti u farmakogenima uključenim u metabolizam vinkristina kod dece obolele od ALL koja su razvila VIPN, u Srbiji. Takođe, cilj nam je bio da otkrijemo kandidate za nove farmakogenomske markere VIPN-a u srpskoj populaciji. Metode Detekcija varijanti gena CYP3A5, CEP72, ACTG1, MIR3117 i MIR4481 izvedena je metodologijom zasnovanom na PCR-u i sekvenciranju. Statističkim metodama je ispitana njihova asocijacija sa VIPN-om kod 56 pedijatrijskih bolesnika obolelih od ALL. Urađena je i populaciona vinkristin farmakogenomska analiza 17 farmakogena iz postojećih podataka dobijenih sekvenciranjem nove generacije u srpskoj populaciji. Podaci o distribuciji frekvencija alela za evropsko stanovništvo preuzeti su iz javnih baza podataka. Rezultati Tokom lečenja, 17,86% bolesnika je razvilo VIPN. Asocijativne analize pokazale su da nijedna genetička varijanta nije bila povezana sa VIPN-om u našoj studiji. Naše populaciono farmakogenomsko istraživanje nije otkrilo validne farmakovarijante za VIPN. Naši rezultati ne preporučuju preventivno farmakogenetičko ispitivanje vinkristina u Srbiji. Zaključak Potreban je sveobuhvatniji pristup kako bi se identifikovao panel gena kojim bi se mogao objasniti razvoj VIPN-a posle primene vinkristina kod pedijatrijskih bolesnika obolelih od ALL. Bolje osmišljene studije asocijacija na nivou genoma (GWAS) i robusniji alati koji koriste veštačku inteligenciju doveli bi do dizajniranja panela farmakogena za preventivno testiranje predispozicije za razvoj VIPN-a, doprinoseći individualizaciji i unapređenju terapije dece obolele od ALL.
AB  - Introduction/Objective Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods PCR and sequencing-based methodology was used to detect variants in CYP3A5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra
T1  - The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia: A single center experience
EP  - 58
IS  - 1-2
SP  - 53
VL  - 150
DO  - 10.2298/SARH210813099R
ER  - 

@article{
author = "Ristivojević, Bojan and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Lazić, Jelena and Pavlović, Sonja and Zukić, Branka",
year = "2022",
abstract = "Uvod/Cilj Vinkristin je jedan od ključnih lekova u protokolima lečenja dečje akutne limfoblastne leukemije (ALL). Vinkristin dovodi do destabilizacije mikrotubula, čime se ćelija zaustavlja u metafazi i indukuje apoptoza. Takođe dovodi do degradacije aksona i poremećaja aksonskog transporta, uzrokujući vinkristinom indukovanu perifernu neuropatiju (VIPN). Cilj ove studije bio je da istraži povezanost pet varijanti u farmakogenima uključenim u metabolizam vinkristina kod dece obolele od ALL koja su razvila VIPN, u Srbiji. Takođe, cilj nam je bio da otkrijemo kandidate za nove farmakogenomske markere VIPN-a u srpskoj populaciji. Metode Detekcija varijanti gena CYP3A5, CEP72, ACTG1, MIR3117 i MIR4481 izvedena je metodologijom zasnovanom na PCR-u i sekvenciranju. Statističkim metodama je ispitana njihova asocijacija sa VIPN-om kod 56 pedijatrijskih bolesnika obolelih od ALL. Urađena je i populaciona vinkristin farmakogenomska analiza 17 farmakogena iz postojećih podataka dobijenih sekvenciranjem nove generacije u srpskoj populaciji. Podaci o distribuciji frekvencija alela za evropsko stanovništvo preuzeti su iz javnih baza podataka. Rezultati Tokom lečenja, 17,86% bolesnika je razvilo VIPN. Asocijativne analize pokazale su da nijedna genetička varijanta nije bila povezana sa VIPN-om u našoj studiji. Naše populaciono farmakogenomsko istraživanje nije otkrilo validne farmakovarijante za VIPN. Naši rezultati ne preporučuju preventivno farmakogenetičko ispitivanje vinkristina u Srbiji. Zaključak Potreban je sveobuhvatniji pristup kako bi se identifikovao panel gena kojim bi se mogao objasniti razvoj VIPN-a posle primene vinkristina kod pedijatrijskih bolesnika obolelih od ALL. Bolje osmišljene studije asocijacija na nivou genoma (GWAS) i robusniji alati koji koriste veštačku inteligenciju doveli bi do dizajniranja panela farmakogena za preventivno testiranje predispozicije za razvoj VIPN-a, doprinoseći individualizaciji i unapređenju terapije dece obolele od ALL., Introduction/Objective Vincristine (VCR) is one of the key drugs in current treatment protocols for pediatric acute lymphoblastic leukemia (ALL). By destabilizing microtubules, VCR arrests cells in metaphase, inducing apoptosis of malignant cells. VCR also causes axonal degradation and impairment of axonal transport, which leads to VCR-induced peripheral neuropathy (VIPN). This study aimed to investigate the association of five variants in pharmacogenes involved in VCR metabolism with VIPN in Serbian ALL children. We also wanted to discover candidate pharmacogenomic markers of VIPN in Serbian population. Methods PCR and sequencing-based methodology was used to detect variants in CYP3A5, CEP72, ACTG1, MIR3117, and MIR4481 genes. Statistical analyses were performed for investigating their association with VIPN in 56 pediatric ALL patients. Population VCR pharmacogenomics analysis of 17 pharmacogenes from in-house next-generation sequencing data was also done. Data on allele frequency distribution for the European population were extracted from public databases. Results During the treatment, 17.86% of patients developed VIPN. Association analyses have shown that none of the genetic variants contributed to the occurrence of VIPN in our study. Population pharmacogenomics study did not reveal valid candidate pharmacovariants for VIPN. Our results suggested that pre-emptive pharmacogenetic testing for VCR is not applicable presently. Conclusion More comprehensive approaches are needed to identify the panel of genes that could explain the VIPN development after VCR administration in ALL patients. Utilizing better designed genome-wide association studies and more robust artificial intelligence-based tools would provide a panel of pharmacogenes for pre-emptive tests of VIPN to individualize therapy for ALL in children.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra, The pharmacogenomics of vincristine-induced peripheral neuropathy in pediatric acute lymphoblastic leukemia patients in Serbia: A single center experience",
pages = "58-53",
number = "1-2",
volume = "150",
doi = "10.2298/SARH210813099R"
}

Ristivojević, B., Kotur, N., Stanković, B., Gašić, V., Lazić, J., Pavlović, S.,& Zukić, B.. (2022). Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 150(1-2), 53-58.
https://doi.org/10.2298/SARH210813099R

Ristivojević B, Kotur N, Stanković B, Gašić V, Lazić J, Pavlović S, Zukić B. Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra. in Srpski arhiv za celokupno lekarstvo. 2022;150(1-2):53-58.
doi:10.2298/SARH210813099R .

Ristivojević, Bojan, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Lazić, Jelena, Pavlović, Sonja, Zukić, Branka, "Farmakogenomika vinkristinom indukovane periferne neuropatije kod dece sa akutnom limfoblastnom leukemijom u Srbiji - iskustvo jednog centra" in Srpski arhiv za celokupno lekarstvo, 150, no. 1-2 (2022):53-58,
https://doi.org/10.2298/SARH210813099R . .

TY  - JOUR
AU  - Pavlović, Đorđe
AU  - Tošić, Nataša
AU  - Zukić, Branka
AU  - Pravdić, Zlatko
AU  - Suvajdžić-Vuković, Nada
AU  - Pavlović, Sonja
AU  - Gašić, Vladimir
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1573
AB  - Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers' attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5(low)/miR-222(high) status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.
PB  - MDPI, Basel
T2  - Diagnostics
T1  - Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients
IS  - 1
VL  - 12
DO  - 10.3390/diagnostics12010086
ER  - 

@article{
author = "Pavlović, Đorđe and Tošić, Nataša and Zukić, Branka and Pravdić, Zlatko and Suvajdžić-Vuković, Nada and Pavlović, Sonja and Gašić, Vladimir",
year = "2022",
abstract = "Acute myeloid leukemia (AML) is a heterogeneous malignant disease both on clinical and genetic levels. AML has poor prognosis and, therefore, there is a constant need to find new prognostic markers, as well as markers that can be used as targets for innovative therapeutics. Recently, the search for new biomarkers has turned researchers' attention towards non-coding RNAs, especially long non-coding RNAs (lncRNAs) and micro RNAs (miRNAs). We investigated the expression level of growth arrest-specific transcript 5 (GAS5) lncRNA in 94 younger AML patients, and also the expression level of miR-222 in a cohort of 39 AML patients with normal karyotype (AML-NK), in order to examine their prognostic potential. Our results showed that GAS5 expression level in AML patients was lower compared to healthy controls. Lower GAS5 expression on diagnosis was related to an adverse prognosis. In the AML-NK group patients had higher expression of miR-222 compared to healthy controls. A synergistic effect of GAS5(low)/miR-222(high) status on disease prognosis was not established. This is the first study focused on examining the GAS5 and miR-222 expression pattern in AML patients. Its initial findings indicate the need for further investigation of these two non-coding RNAs, their potential roles in leukemogenesis, and the prognosis of AML patients.",
publisher = "MDPI, Basel",
journal = "Diagnostics",
title = "Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients",
number = "1",
volume = "12",
doi = "10.3390/diagnostics12010086"
}

Pavlović, Đ., Tošić, N., Zukić, B., Pravdić, Z., Suvajdžić-Vuković, N., Pavlović, S.,& Gašić, V.. (2022). Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients. in Diagnostics
MDPI, Basel., 12(1).
https://doi.org/10.3390/diagnostics12010086

Pavlović Đ, Tošić N, Zukić B, Pravdić Z, Suvajdžić-Vuković N, Pavlović S, Gašić V. Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients. in Diagnostics. 2022;12(1).
doi:10.3390/diagnostics12010086 .

Pavlović, Đorđe, Tošić, Nataša, Zukić, Branka, Pravdić, Zlatko, Suvajdžić-Vuković, Nada, Pavlović, Sonja, Gašić, Vladimir, "Expression Profiles of Long Non-Coding RNA GAS5 and MicroRNA-222 in Younger AML Patients" in Diagnostics, 12, no. 1 (2022),
https://doi.org/10.3390/diagnostics12010086 . .

TY  - JOUR
AU  - Gašić, Vladimir
AU  - Karan-Đurašević, Teodora
AU  - Pavlović, Đorđe
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Tošić, Nataša
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1660
AB  - Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.
T2  - Life
T2  - Life
T1  - Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia
IS  - 11
SP  - 1770
VL  - 12
DO  - 10.3390/life12111770
ER  - 

@article{
author = "Gašić, Vladimir and Karan-Đurašević, Teodora and Pavlović, Đorđe and Zukić, Branka and Pavlović, Sonja and Tošić, Nataša",
year = "2022",
abstract = "Leukemia is a heterogenous group of hematological malignancies categorized in four main types (acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Several cytogenetic and molecular markers have become a part of routine analysis for leukemia patients. These markers have been used in diagnosis, risk-stratification and targeted therapy application. Recent studies have indicated that numerous regulatory RNAs, such as long non-coding RNAs (lncRNAs), have a role in tumor initiation and progression. When it comes to leukemia, data for lncRNA involvement in its etiology, progression, diagnosis, treatment and prognosis is limited. The aim of this review is to summarize research data on lncRNAs in different types of leukemia, on their expression pattern, their role in leukemic transformation and disease progression. The usefulness of this information in the clinical setting, i.e., for diagnostic and prognostic purposes, will be emphasized. Finally, how particular lncRNAs could be used as potential targets for the application of targeted therapy will be considered.",
journal = "Life, Life",
title = "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia",
number = "11",
pages = "1770",
volume = "12",
doi = "10.3390/life12111770"
}

Gašić, V., Karan-Đurašević, T., Pavlović, Đ., Zukić, B., Pavlović, S.,& Tošić, N.. (2022). Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life, 12(11), 1770.
https://doi.org/10.3390/life12111770

Gašić V, Karan-Đurašević T, Pavlović Đ, Zukić B, Pavlović S, Tošić N. Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia. in Life. 2022;12(11):1770.
doi:10.3390/life12111770 .

Gašić, Vladimir, Karan-Đurašević, Teodora, Pavlović, Đorđe, Zukić, Branka, Pavlović, Sonja, Tošić, Nataša, "Diagnostic and Therapeutic Implications of Long Non-Coding RNAs in Leukemia" in Life, 12, no. 11 (2022):1770,
https://doi.org/10.3390/life12111770 . .

TY  - JOUR
AU  - Zecević, Marko
AU  - Kotur, Nikola
AU  - Ristivojević, Bojan
AU  - Gašić, Vladimir
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Zukić, Branka
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1515
AB  - Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 x 10(-8)). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 10(-6)). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Genetics
T1  - Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population
VL  - 13
DO  - 10.3389/fgene.2022.911010
ER  - 

@article{
author = "Zecević, Marko and Kotur, Nikola and Ristivojević, Bojan and Gašić, Vladimir and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Stevanović, Goran and Lavadinović, Lidija and Zukić, Branka and Pavlović, Sonja and Stanković, Biljana",
year = "2022",
abstract = "Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 x 10(-8)). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 x 10(-6)) and severe COVID-19 (p = 6.88 x 10(-7)), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 x 10(-6)), 5q11.2 (ESM1, p = 6.59 x 10(-6)), and 9p23 (TYRP1, LURAP1L, p = 8.69 x 10(-6)). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Genetics",
title = "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population",
volume = "13",
doi = "10.3389/fgene.2022.911010"
}

Zecević, M., Kotur, N., Ristivojević, B., Gašić, V., Skodrić-Trifunović, V., Stjepanović, M., Stevanović, G., Lavadinović, L., Zukić, B., Pavlović, S.,& Stanković, B.. (2022). Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics
Frontiers Media Sa, Lausanne., 13.
https://doi.org/10.3389/fgene.2022.911010

Zecević M, Kotur N, Ristivojević B, Gašić V, Skodrić-Trifunović V, Stjepanović M, Stevanović G, Lavadinović L, Zukić B, Pavlović S, Stanković B. Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population. in Frontiers in Genetics. 2022;13.
doi:10.3389/fgene.2022.911010 .

Zecević, Marko, Kotur, Nikola, Ristivojević, Bojan, Gašić, Vladimir, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Stevanović, Goran, Lavadinović, Lidija, Zukić, Branka, Pavlović, Sonja, Stanković, Biljana, "Genome-Wide Association Study of COVID-19 Outcomes Reveals Novel Host Genetic Risk Loci in the Serbian Population" in Frontiers in Genetics, 13 (2022),
https://doi.org/10.3389/fgene.2022.911010 . .

TY  - CONF
AU  - Klaassen, Kristel
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Pavlović, Sonja
AU  - Stojiljković, Maja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1577
PB  - Springernature, London
C3  - European Journal of Human Genetics
T1  - Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection
EP  - 603
IS  - SUPPL 1
SP  - 603
VL  - 30
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1577
ER  - 

@conference{
author = "Klaassen, Kristel and Stanković, Biljana and Zukić, Branka and Kotur, Nikola and Gašić, Vladimir and Pavlović, Sonja and Stojiljković, Maja",
year = "2022",
publisher = "Springernature, London",
journal = "European Journal of Human Genetics",
title = "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection",
pages = "603-603",
number = "SUPPL 1",
volume = "30",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1577"
}

Klaassen, K., Stanković, B., Zukić, B., Kotur, N., Gašić, V., Pavlović, S.,& Stojiljković, M.. (2022). Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in European Journal of Human Genetics
Springernature, London., 30(SUPPL 1), 603-603.
https://hdl.handle.net/21.15107/rcub_imagine_1577

Klaassen K, Stanković B, Zukić B, Kotur N, Gašić V, Pavlović S, Stojiljković M. Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in European Journal of Human Genetics. 2022;30(SUPPL 1):603-603.
https://hdl.handle.net/21.15107/rcub_imagine_1577 .

Klaassen, Kristel, Stanković, Biljana, Zukić, Branka, Kotur, Nikola, Gašić, Vladimir, Pavlović, Sonja, Stojiljković, Maja, "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection" in European Journal of Human Genetics, 30, no. SUPPL 1 (2022):603-603,
https://hdl.handle.net/21.15107/rcub_imagine_1577 .

TY  - CHAP
AU  - Gašić, Vladimir
AU  - Pavlović, Đorđe
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1620
AB  - Pharmacogenomics and pharmacotranscriptomics contribute to more efficient and safer treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy during childhood. Glucocorticoids, prednisone and dexamethasone, represent the basis of chemotherapy in pediatric ALL. Therapy causes side effects in 75% of patients and 1–3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. There is a growing knowledge of pharmacogenomics and pharmacotranscriptomics markers relevant for the success of the glucocorticoid treatment of children with ALL. New technologies, such as next-generation sequencing (NGS) have created a possibility for designing panels of pharmacogenomics and pharmacotranscriptomics markers related to the response to glucocorticoid drugs. Optimization of these panels through population pharmacogenomic studies leads to new knowledge that could open the doors widely to pre-emptive pharmacogenomic testing.
PB  - IntechOpen
T2  - Corticosteroids : A Paradigmatic Drug Class
T2  - glucocorticoids
T2  - pediatric acute lymphoblastic leukemia
T2  - pharmacogenomics
T2  - pharmacotranscriptomics
T2  - population pharmacogenomics
T1  - Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia
EP  - 17
SP  - 1
DO  - 10.5772/intechopen.98887
ER  - 

@inbook{
author = "Gašić, Vladimir and Pavlović, Đorđe and Stanković, Biljana and Kotur, Nikola and Zukić, Branka and Pavlović, Sonja",
year = "2021",
abstract = "Pharmacogenomics and pharmacotranscriptomics contribute to more efficient and safer treatment of many diseases, especially malignancies. Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy during childhood. Glucocorticoids, prednisone and dexamethasone, represent the basis of chemotherapy in pediatric ALL. Therapy causes side effects in 75% of patients and 1–3% of pediatric ALL patients die because of therapy side effects rather than the disease itself. Due to this fact, pharmacogenomics and pharmacotranscriptomics have gained key positions in this field. There is a growing knowledge of pharmacogenomics and pharmacotranscriptomics markers relevant for the success of the glucocorticoid treatment of children with ALL. New technologies, such as next-generation sequencing (NGS) have created a possibility for designing panels of pharmacogenomics and pharmacotranscriptomics markers related to the response to glucocorticoid drugs. Optimization of these panels through population pharmacogenomic studies leads to new knowledge that could open the doors widely to pre-emptive pharmacogenomic testing.",
publisher = "IntechOpen",
journal = "Corticosteroids : A Paradigmatic Drug Class, glucocorticoids, pediatric acute lymphoblastic leukemia, pharmacogenomics, pharmacotranscriptomics, population pharmacogenomics",
booktitle = "Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia",
pages = "17-1",
doi = "10.5772/intechopen.98887"
}

Gašić, V., Pavlović, Đ., Stanković, B., Kotur, N., Zukić, B.,& Pavlović, S.. (2021). Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia. in Corticosteroids : A Paradigmatic Drug Class
IntechOpen., 1-17.
https://doi.org/10.5772/intechopen.98887

Gašić V, Pavlović Đ, Stanković B, Kotur N, Zukić B, Pavlović S. Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia. in Corticosteroids : A Paradigmatic Drug Class. 2021;:1-17.
doi:10.5772/intechopen.98887 .

Gašić, Vladimir, Pavlović, Đorđe, Stanković, Biljana, Kotur, Nikola, Zukić, Branka, Pavlović, Sonja, "Pharmacogenomics and pharmacotranscriptomics of glucocorticoids in pediatric acute lymphoblastic leukemia" in Corticosteroids : A Paradigmatic Drug Class (2021):1-17,
https://doi.org/10.5772/intechopen.98887 . .

TY  - JOUR
AU  - Kotur, Nikola
AU  - Skakić, Anita
AU  - Klaassen, Kristel
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Skodrić-Trifunović, Vesna
AU  - Stjepanović, Mihailo
AU  - Zivković, Zorica
AU  - Ostojić, Olivera
AU  - Stevanović, Goran
AU  - Lavadinović, Lidija
AU  - Pavlović, Sonja
AU  - Stanković, Biljana
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1439
AB  - Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Nutrition
T1  - Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
VL  - 8
DO  - 10.3389/fnut.2021.689419
ER  - 

@article{
author = "Kotur, Nikola and Skakić, Anita and Klaassen, Kristel and Gašić, Vladimir and Zukić, Branka and Skodrić-Trifunović, Vesna and Stjepanović, Mihailo and Zivković, Zorica and Ostojić, Olivera and Stevanović, Goran and Lavadinović, Lidija and Pavlović, Sonja and Stanković, Biljana",
year = "2021",
abstract = "Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19. Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants. Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05-0.9) and OR 5.9 (1.4-25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course. Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Nutrition",
title = "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity",
volume = "8",
doi = "10.3389/fnut.2021.689419"
}

Kotur, N., Skakić, A., Klaassen, K., Gašić, V., Zukić, B., Skodrić-Trifunović, V., Stjepanović, M., Zivković, Z., Ostojić, O., Stevanović, G., Lavadinović, L., Pavlović, S.,& Stanković, B.. (2021). Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition
Frontiers Media Sa, Lausanne., 8.
https://doi.org/10.3389/fnut.2021.689419

Kotur N, Skakić A, Klaassen K, Gašić V, Zukić B, Skodrić-Trifunović V, Stjepanović M, Zivković Z, Ostojić O, Stevanović G, Lavadinović L, Pavlović S, Stanković B. Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity. in Frontiers in Nutrition. 2021;8.
doi:10.3389/fnut.2021.689419 .

Kotur, Nikola, Skakić, Anita, Klaassen, Kristel, Gašić, Vladimir, Zukić, Branka, Skodrić-Trifunović, Vesna, Stjepanović, Mihailo, Zivković, Zorica, Ostojić, Olivera, Stevanović, Goran, Lavadinović, Lidija, Pavlović, Sonja, Stanković, Biljana, "Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity" in Frontiers in Nutrition, 8 (2021),
https://doi.org/10.3389/fnut.2021.689419 . .

TY  - CHAP
AU  - Gašić, Vladimir
AU  - Tošić, Nataša
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1727
AB  - Growth arrest specific 5 (GAS5) je duga nekodirajuća RNK koja zaustavlja ćelijski ciklus i promoviše apoptozu.
Ponašajući se kao signalni protein, kao mamac za druge molekule ili kao transportni molekul, ova regulatorna
RNK utiče na niz puteva i molekula koji su bitni za rast ćelije i apoptozu, među kojima se ističu p53 mreža,
mTOR signalni put, AKT signalni put, kao i molekuli mikro RNK, PTEN i slični. Brojne studije na različitim tipovima
karcinoma su pokazale da nivo ekspresije GAS5 utiče na razvoj i tok bolesti kod hematoloških maligniteta,
ginekoloških karcinoma, glioma, karcinoma dojke, karcinoma gastrointestinalnog trakta, bubrega,
bešike, prostate i pluća. Shodno tome, GAS5 je novi biomarker u onkologiji, koji ima dijagnostički i prognostički
značaj.
AB  - Growth arrest specific 5 (GAS5) is a long noncoding RNA which halts the cell cycle and promotes apoptosis.
Acting as a signal protein, as a decoy for other molecules or as a transport molecule, this regulatory RNA influences
a number of pathways and molecules relevant for the growth of the cell and apoptosis, among
them the most important being the p53 network, the mTOR signal pathway, the AKT signal pathway, as well
as molecules of microRNA, PTEN and others.
Numerous studies on diverse cancer types have confirmed that the expression of GAS5 influences the development
and the course of hematological malignancies, gynecologic carcinoma, gliomas, breast cancer,
gastrointestinal cancer, kidney cancer, bladder cancer, prostate cancer and lung cancer. Therefore, GAS5 is
a promising new diagnostic and prognostic biomarker in oncology.
PB  - Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo
T2  - Trendovi u molekularnoj Biologiji
T1  - Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji
T1  - long noncoding rna gaS as a new biomarker in oncology
EP  - 122
SP  - 113
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1727
ER  - 

@inbook{
author = "Gašić, Vladimir and Tošić, Nataša",
year = "2021",
abstract = "Growth arrest specific 5 (GAS5) je duga nekodirajuća RNK koja zaustavlja ćelijski ciklus i promoviše apoptozu.
Ponašajući se kao signalni protein, kao mamac za druge molekule ili kao transportni molekul, ova regulatorna
RNK utiče na niz puteva i molekula koji su bitni za rast ćelije i apoptozu, među kojima se ističu p53 mreža,
mTOR signalni put, AKT signalni put, kao i molekuli mikro RNK, PTEN i slični. Brojne studije na različitim tipovima
karcinoma su pokazale da nivo ekspresije GAS5 utiče na razvoj i tok bolesti kod hematoloških maligniteta,
ginekoloških karcinoma, glioma, karcinoma dojke, karcinoma gastrointestinalnog trakta, bubrega,
bešike, prostate i pluća. Shodno tome, GAS5 je novi biomarker u onkologiji, koji ima dijagnostički i prognostički
značaj., Growth arrest specific 5 (GAS5) is a long noncoding RNA which halts the cell cycle and promotes apoptosis.
Acting as a signal protein, as a decoy for other molecules or as a transport molecule, this regulatory RNA influences
a number of pathways and molecules relevant for the growth of the cell and apoptosis, among
them the most important being the p53 network, the mTOR signal pathway, the AKT signal pathway, as well
as molecules of microRNA, PTEN and others.
Numerous studies on diverse cancer types have confirmed that the expression of GAS5 influences the development
and the course of hematological malignancies, gynecologic carcinoma, gliomas, breast cancer,
gastrointestinal cancer, kidney cancer, bladder cancer, prostate cancer and lung cancer. Therefore, GAS5 is
a promising new diagnostic and prognostic biomarker in oncology.",
publisher = "Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo",
journal = "Trendovi u molekularnoj Biologiji",
booktitle = "Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji, long noncoding rna gaS as a new biomarker in oncology",
pages = "122-113",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1727"
}

Gašić, V.,& Tošić, N.. (2021). Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji. in Trendovi u molekularnoj Biologiji
Beograd : Institut za molekularnu genetiku i genetičko inženjerstvo., 113-122.
https://hdl.handle.net/21.15107/rcub_imagine_1727

Gašić V, Tošić N. Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji. in Trendovi u molekularnoj Biologiji. 2021;:113-122.
https://hdl.handle.net/21.15107/rcub_imagine_1727 .

Gašić, Vladimir, Tošić, Nataša, "Duga nekodirajuća rnk gaS kao novi biomarker u onkologiji" in Trendovi u molekularnoj Biologiji (2021):113-122,
https://hdl.handle.net/21.15107/rcub_imagine_1727 .

TY  - JOUR
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Nikčević, Gordana
AU  - Gašić, Vladimir
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1460
AB  - Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials.
PB  - MDPI, Basel
T2  - Genes
T1  - Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications
IS  - 9
VL  - 12
DO  - 10.3390/genes12091438
ER  - 

@article{
author = "Stanković, Biljana and Kotur, Nikola and Nikčević, Gordana and Gašić, Vladimir and Zukić, Branka and Pavlović, Sonja",
year = "2021",
abstract = "Research of inflammatory bowel disease (IBD) has identified numerous molecular players involved in the disease development. Even so, the understanding of IBD is incomplete, while disease treatment is still far from the precision medicine. Reliable diagnostic and prognostic biomarkers in IBD are limited which may reduce efficient therapeutic outcomes. High-throughput technologies and artificial intelligence emerged as powerful tools in search of unrevealed molecular patterns that could give important insights into IBD pathogenesis and help to address unmet clinical needs. Machine learning, a subtype of artificial intelligence, uses complex mathematical algorithms to learn from existing data in order to predict future outcomes. The scientific community has been increasingly employing machine learning for the prediction of IBD outcomes from comprehensive patient data-clinical records, genomic, transcriptomic, proteomic, metagenomic, and other IBD relevant omics data. This review aims to present fundamental principles behind machine learning modeling and its current application in IBD research with the focus on studies that explored genomic and transcriptomic data. We described different strategies used for dealing with omics data and outlined the best-performing methods. Before being translated into clinical settings, the developed machine learning models should be tested in independent prospective studies as well as randomized controlled trials.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications",
number = "9",
volume = "12",
doi = "10.3390/genes12091438"
}

Stanković, B., Kotur, N., Nikčević, G., Gašić, V., Zukić, B.,& Pavlović, S.. (2021). Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications. in Genes
MDPI, Basel., 12(9).
https://doi.org/10.3390/genes12091438

Stanković B, Kotur N, Nikčević G, Gašić V, Zukić B, Pavlović S. Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications. in Genes. 2021;12(9).
doi:10.3390/genes12091438 .

Stanković, Biljana, Kotur, Nikola, Nikčević, Gordana, Gašić, Vladimir, Zukić, Branka, Pavlović, Sonja, "Machine Learning Modeling from Omics Data as Prospective Tool for Improvement of Inflammatory Bowel Disease Diagnosis and Clinical Classifications" in Genes, 12, no. 9 (2021),
https://doi.org/10.3390/genes12091438 . .

TY  - JOUR
AU  - Mihaljević, Marina
AU  - Franić, Dusanka
AU  - Soldatović, Ivan
AU  - Lukić, Iva
AU  - Andrić-Petrović, Sanja
AU  - Mirjanić, Tijana
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Zeljić, Katarina
AU  - Gašić, Vladimir
AU  - Novaković, Ivana
AU  - Pavlović, Sonja
AU  - Adžić, Miroslav
AU  - Marić, Nadja P.
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1451
AB  - Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Psychoneuroendocrinology
T1  - The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls
VL  - 128
DO  - 10.1016/j.psyneuen.2021.105205
ER  - 

@article{
author = "Mihaljević, Marina and Franić, Dusanka and Soldatović, Ivan and Lukić, Iva and Andrić-Petrović, Sanja and Mirjanić, Tijana and Stanković, Biljana and Zukić, Branka and Zeljić, Katarina and Gašić, Vladimir and Novaković, Ivana and Pavlović, Sonja and Adžić, Miroslav and Marić, Nadja P.",
year = "2021",
abstract = "Hypothalamic-pituitary-adrenal (HPA) axis activity mediates the relationship between childhood trauma (CT) and psychosis. The FKBP5 gene, one of the key regulators of HPA axis activity after stress exposure, has been found associated with psychosis. Allele-specific and CT related FKBP5 demethylation in intron 7 was revealed in different psychiatric disorders. However, no studies have investigated FKBP5 methylation in subjects with different genetic liability for psychosis. A total of 144 participants were included in the study: 48 patients with psychotic disorders, 50 unaffected siblings, and 46 healthy controls. CT was assessed by Childhood Trauma Questionnaire. The FKBP5 rs1360780 was genotyped and FKBP5 methylation analyses were performed using bisulfite conversion followed by Sanger sequencing at three CpG sites in intron 7. Mixed linear model was used to assess group differences depending on rs1360780 T allele and CT. Results showed a significant T allele-dependent decrease of FKBP5 methylation in patients compared to unaffected siblings and controls. Effect of interaction between T allele and CT exposure on FKBP5 demethylation was found in controls. No effect of both risk factors (T allele and CT) on FKBP5 methylation level was found in unaffected siblings. We confirmed previous evidence of the association between the FKBP5 rs1360780 T allele, CT, and decreased FKBP5 methylation in intron 7. Allele-specific FKBP5 demethylation found in patients could shed a light on altered HPA axis activity in a subgroup of patients related to stress-induced psychosis. FKBP5 methylation and potential protective mechanisms in unaffected siblings after trauma exposure require further investigation.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Psychoneuroendocrinology",
title = "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls",
volume = "128",
doi = "10.1016/j.psyneuen.2021.105205"
}

Mihaljević, M., Franić, D., Soldatović, I., Lukić, I., Andrić-Petrović, S., Mirjanić, T., Stanković, B., Zukić, B., Zeljić, K., Gašić, V., Novaković, I., Pavlović, S., Adžić, M.,& Marić, N. P.. (2021). The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology
Pergamon-Elsevier Science Ltd, Oxford., 128.
https://doi.org/10.1016/j.psyneuen.2021.105205

Mihaljević M, Franić D, Soldatović I, Lukić I, Andrić-Petrović S, Mirjanić T, Stanković B, Zukić B, Zeljić K, Gašić V, Novaković I, Pavlović S, Adžić M, Marić NP. The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls. in Psychoneuroendocrinology. 2021;128.
doi:10.1016/j.psyneuen.2021.105205 .

Mihaljević, Marina, Franić, Dusanka, Soldatović, Ivan, Lukić, Iva, Andrić-Petrović, Sanja, Mirjanić, Tijana, Stanković, Biljana, Zukić, Branka, Zeljić, Katarina, Gašić, Vladimir, Novaković, Ivana, Pavlović, Sonja, Adžić, Miroslav, Marić, Nadja P., "The FKBP5 genotype and childhood trauma effects on FKBP5 DNA methylation in patients with psychosis, their unaffected siblings, and healthy controls" in Psychoneuroendocrinology, 128 (2021),
https://doi.org/10.1016/j.psyneuen.2021.105205 . .

TY  - JOUR
AU  - Kotur, Nikola
AU  - Lazić, Jelena
AU  - Ristivojević, Bojan
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Dokmanović, Lidija
AU  - Krstovski, Nada
AU  - Milosević, Goran
AU  - Janić, Dragana
AU  - Zukić, Branka
AU  - Pavlović, Sonja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1322
AB  - Methotrexate (MTX) is one of the staples of pediatric acute lymphoblastic leukemia (ALL) treatment. MTX targets the folate metabolic pathway (FMP). Abnormal function of the enzymes in FMP, due to genetic aberrations, leads to adverse drug reactions. The aim of this study was to investigate variants in pharmacogenes involved in FMP and their association with MTX pharmacokinetics (MTX elimination profile) and toxicity in the consolidation therapy phase of pediatric ALL patients. Eleven variants in the thymidylate synthetase (TYMS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), SLC19A1 and SLCO1B genes were analyzed in 148 patients, using PCR- and sequencing-based methodology. For the Serbian and European control groups, data on allele frequency distribution were extracted from in-house and public databases. Our results show that the A allele of SLC19A1 c.80 variant contributes to slow MTX elimination. Additionally, the AA genotype of the same variant is a predictor of MTX-related hepatotoxicity. Patients homozygous for TYMS 6bp deletion were more likely to experience gastrointestinal toxicity. No allele frequency dissimilarity was found for the analyzed variants between Serbian and European populations. Statistical modelling did not show a joint effect of analyzed variants. Our results indicate that SLC19A1 c.80 variant and TYMS 6bp deletion are the most promising pharmacogenomic markers of MTX response in pediatric ALL patients.
PB  - MDPI, Basel
T2  - Genes
T1  - Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment
IS  - 4
VL  - 11
DO  - 10.3390/genes11040468
ER  - 

@article{
author = "Kotur, Nikola and Lazić, Jelena and Ristivojević, Bojan and Stanković, Biljana and Gašić, Vladimir and Dokmanović, Lidija and Krstovski, Nada and Milosević, Goran and Janić, Dragana and Zukić, Branka and Pavlović, Sonja",
year = "2020",
abstract = "Methotrexate (MTX) is one of the staples of pediatric acute lymphoblastic leukemia (ALL) treatment. MTX targets the folate metabolic pathway (FMP). Abnormal function of the enzymes in FMP, due to genetic aberrations, leads to adverse drug reactions. The aim of this study was to investigate variants in pharmacogenes involved in FMP and their association with MTX pharmacokinetics (MTX elimination profile) and toxicity in the consolidation therapy phase of pediatric ALL patients. Eleven variants in the thymidylate synthetase (TYMS), methylenetetrahydrofolate reductase (MTHFR), dihydrofolate reductase (DHFR), SLC19A1 and SLCO1B genes were analyzed in 148 patients, using PCR- and sequencing-based methodology. For the Serbian and European control groups, data on allele frequency distribution were extracted from in-house and public databases. Our results show that the A allele of SLC19A1 c.80 variant contributes to slow MTX elimination. Additionally, the AA genotype of the same variant is a predictor of MTX-related hepatotoxicity. Patients homozygous for TYMS 6bp deletion were more likely to experience gastrointestinal toxicity. No allele frequency dissimilarity was found for the analyzed variants between Serbian and European populations. Statistical modelling did not show a joint effect of analyzed variants. Our results indicate that SLC19A1 c.80 variant and TYMS 6bp deletion are the most promising pharmacogenomic markers of MTX response in pediatric ALL patients.",
publisher = "MDPI, Basel",
journal = "Genes",
title = "Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment",
number = "4",
volume = "11",
doi = "10.3390/genes11040468"
}

Kotur, N., Lazić, J., Ristivojević, B., Stanković, B., Gašić, V., Dokmanović, L., Krstovski, N., Milosević, G., Janić, D., Zukić, B.,& Pavlović, S.. (2020). Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment. in Genes
MDPI, Basel., 11(4).
https://doi.org/10.3390/genes11040468

Kotur N, Lazić J, Ristivojević B, Stanković B, Gašić V, Dokmanović L, Krstovski N, Milosević G, Janić D, Zukić B, Pavlović S. Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment. in Genes. 2020;11(4).
doi:10.3390/genes11040468 .

Kotur, Nikola, Lazić, Jelena, Ristivojević, Bojan, Stanković, Biljana, Gašić, Vladimir, Dokmanović, Lidija, Krstovski, Nada, Milosević, Goran, Janić, Dragana, Zukić, Branka, Pavlović, Sonja, "Pharmacogenomic Markers of Methotrexate Response in the Consolidation Phase of Pediatric Acute Lymphoblastic Leukemia Treatment" in Genes, 11, no. 4 (2020),
https://doi.org/10.3390/genes11040468 . .

TY  - JOUR
AU  - Klaassen, Kristel
AU  - Stanković, Biljana
AU  - Zukić, Branka
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Pavlović, Sonja
AU  - Stojiljković, Maja
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1350
AB  - New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.
PB  - Elsevier, Amsterdam
T2  - Infection Genetics and Evolution
T1  - Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection
VL  - 84
DO  - 10.1016/j.meegid.2020.104498
ER  - 

@article{
author = "Klaassen, Kristel and Stanković, Biljana and Zukić, Branka and Kotur, Nikola and Gašić, Vladimir and Pavlović, Sonja and Stojiljković, Maja",
year = "2020",
abstract = "New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.",
publisher = "Elsevier, Amsterdam",
journal = "Infection Genetics and Evolution",
title = "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection",
volume = "84",
doi = "10.1016/j.meegid.2020.104498"
}

Klaassen, K., Stanković, B., Zukić, B., Kotur, N., Gašić, V., Pavlović, S.,& Stojiljković, M.. (2020). Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in Infection Genetics and Evolution
Elsevier, Amsterdam., 84.
https://doi.org/10.1016/j.meegid.2020.104498

Klaassen K, Stanković B, Zukić B, Kotur N, Gašić V, Pavlović S, Stojiljković M. Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection. in Infection Genetics and Evolution. 2020;84.
doi:10.1016/j.meegid.2020.104498 .

Klaassen, Kristel, Stanković, Biljana, Zukić, Branka, Kotur, Nikola, Gašić, Vladimir, Pavlović, Sonja, Stojiljković, Maja, "Functional prediction and comparative population analysis of variants in genes for proteases and innate immunity related to SARS-CoV-2 infection" in Infection Genetics and Evolution, 84 (2020),
https://doi.org/10.1016/j.meegid.2020.104498 . .

TY  - JOUR
AU  - Zukić, Branka
AU  - Anđelković, Marina
AU  - Gašić, Vladimir
AU  - Grubin, Jasmina
AU  - Pavlović, Sonja
AU  - Đerić, Dragoslava
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1357
AB  - Uvod Otoskleroza je poremećaj koštane kapsule lavirinta i slušnih koščica uva, koji dovodi do gubitka sluha zbog nemogućnosti provođenja zvuka. Genetički uzrok otoskleroze je nepoznat. Cilj ovog rada je bio da se sačini sveobuhvatni pregled savremenih saznanja o genetičkoj osnovi otoskleroze. Metode Za prikaz podataka o genetici otoskleroze korišćen je narativni pregled literature. Rezultati Genetika otoskleroze nije mnogo izučavana i literaturni podaci o genetičkoj osnovi otoskleroze su oskudni. Međutim, u novije vreme, proširuju se znanja o genetičkoj osnovi otoskleroze. Ovde je prikazan pregled znanja o asocijaciji genetičkih markera i otoskleroze, koja su rezultat analiza genetičke povezanosti, kao i asocijativnih studija gena kandidata i sveobuhvatnih analiza genoma. Zaključak Otoskleroza zbog svoje kompleksnosti nije bolest čija će genetička osnova biti lako rasvetljena. Analize omika i bioinformatika će doprineti razumevanju genetičke osnove otoskleroze.
AB  - Introduction Otosclerosis is a disorder of the bone labyrinth and stapes resulting in conductive hearing loss. The genetic basis of otosclerosis still remains unknown. We aimed at reporting a comprehensive review of up-to-date knowledge on genetic basis of otosclerosis. Methods Narrative literature review was undertaken to summarize the data about genetics of otosclerosis. Results Genetics of otosclerosis has not been studied extensively and the literature on this topic is scarce. However, knowledge of genetic basis of otosclerosis is recently increasing. We have presented an overview of the knowledge of association of genetic markers with otosclerosis, gained from linkage analyses, candidate-gene studies, and modern high-throughput genomic studies. Conclusion Due to its complex pathophysiology, otosclerosis is not a disease whose genetic base will be easily understood. Multiple omics analysis and bioinformatics will lead to elucidation of genetic basis of otosclerosis.
PB  - Srpsko lekarsko društvo, Beograd
T2  - Srpski arhiv za celokupno lekarstvo
T1  - Genetička osnova otoskleroze
T1  - Genetic basis of otosclerosis
EP  - 625
IS  - 9-10
SP  - 621
VL  - 148
DO  - 10.2298/SARH200306026Z
ER  - 

@article{
author = "Zukić, Branka and Anđelković, Marina and Gašić, Vladimir and Grubin, Jasmina and Pavlović, Sonja and Đerić, Dragoslava",
year = "2020",
abstract = "Uvod Otoskleroza je poremećaj koštane kapsule lavirinta i slušnih koščica uva, koji dovodi do gubitka sluha zbog nemogućnosti provođenja zvuka. Genetički uzrok otoskleroze je nepoznat. Cilj ovog rada je bio da se sačini sveobuhvatni pregled savremenih saznanja o genetičkoj osnovi otoskleroze. Metode Za prikaz podataka o genetici otoskleroze korišćen je narativni pregled literature. Rezultati Genetika otoskleroze nije mnogo izučavana i literaturni podaci o genetičkoj osnovi otoskleroze su oskudni. Međutim, u novije vreme, proširuju se znanja o genetičkoj osnovi otoskleroze. Ovde je prikazan pregled znanja o asocijaciji genetičkih markera i otoskleroze, koja su rezultat analiza genetičke povezanosti, kao i asocijativnih studija gena kandidata i sveobuhvatnih analiza genoma. Zaključak Otoskleroza zbog svoje kompleksnosti nije bolest čija će genetička osnova biti lako rasvetljena. Analize omika i bioinformatika će doprineti razumevanju genetičke osnove otoskleroze., Introduction Otosclerosis is a disorder of the bone labyrinth and stapes resulting in conductive hearing loss. The genetic basis of otosclerosis still remains unknown. We aimed at reporting a comprehensive review of up-to-date knowledge on genetic basis of otosclerosis. Methods Narrative literature review was undertaken to summarize the data about genetics of otosclerosis. Results Genetics of otosclerosis has not been studied extensively and the literature on this topic is scarce. However, knowledge of genetic basis of otosclerosis is recently increasing. We have presented an overview of the knowledge of association of genetic markers with otosclerosis, gained from linkage analyses, candidate-gene studies, and modern high-throughput genomic studies. Conclusion Due to its complex pathophysiology, otosclerosis is not a disease whose genetic base will be easily understood. Multiple omics analysis and bioinformatics will lead to elucidation of genetic basis of otosclerosis.",
publisher = "Srpsko lekarsko društvo, Beograd",
journal = "Srpski arhiv za celokupno lekarstvo",
title = "Genetička osnova otoskleroze, Genetic basis of otosclerosis",
pages = "625-621",
number = "9-10",
volume = "148",
doi = "10.2298/SARH200306026Z"
}

Zukić, B., Anđelković, M., Gašić, V., Grubin, J., Pavlović, S.,& Đerić, D.. (2020). Genetička osnova otoskleroze. in Srpski arhiv za celokupno lekarstvo
Srpsko lekarsko društvo, Beograd., 148(9-10), 621-625.
https://doi.org/10.2298/SARH200306026Z

Zukić B, Anđelković M, Gašić V, Grubin J, Pavlović S, Đerić D. Genetička osnova otoskleroze. in Srpski arhiv za celokupno lekarstvo. 2020;148(9-10):621-625.
doi:10.2298/SARH200306026Z .

Zukić, Branka, Anđelković, Marina, Gašić, Vladimir, Grubin, Jasmina, Pavlović, Sonja, Đerić, Dragoslava, "Genetička osnova otoskleroze" in Srpski arhiv za celokupno lekarstvo, 148, no. 9-10 (2020):621-625,
https://doi.org/10.2298/SARH200306026Z . .

TY  - JOUR
AU  - Stanković, Biljana
AU  - Kotur, Nikola
AU  - Gašić, Vladimir
AU  - Klaassen, Kristel
AU  - Ristivojević, Bojan
AU  - Stojiljković, Maja
AU  - Pavlović, Sonja
AU  - Zukić, Branka
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1362
AB  - Uvod: Kako ne postoje odobreni terapeutici za lečenje pacijenata sa COVID-19, mogućnost upotrebe postojećih lekova je postala važna. U nedostatku vremena za testiranje farmakogenomskih markera kod pojedinaca, populaciona farmakogenomika bi mogla biti od koristi u predviđanju povećanog rizika za pojavu neželjenih reakcija i neuspeha lečenja kod pacijenata sa COVID-19. Cilj naše studije bio je identifikovanje farmakogena i farmakogenomskih markera povezanih sa lekovima koji se preporučuju za lečenje COVID-19, hlorokin/hidroksihlorokin, azitromicin, lopinavir i ritonavir, u populaciji Srbije i drugim svetskim populacijama. Metode: Podaci o genotipu 143 osobe srpskog porekla dobijeni su iz baze podataka prethodno formirane analizama genoma korišćenjem TruSight One Gene Panel (Illumina). Podaci o genotipu pojedinaca iz različitih svetskih populacija dobijeni su iz Projekta 1000 genoma. Fišerov egzaktni test korišćen je za poređenje učestalosti alela. Rezultati: Identifikovali smo 11 potencijalnih farmakogenomskih markera u 7 farmakogena značajnih za lečenje COVID-19. Na osnovu visoke alterativne učestalosti alela u populaciji Srbije i funkcionalnog efekta varijanti, ABCB1 rs1045642 i rs2032582 mogu biti značajne za smanjeni klirens lekova azitromicina, lopinavira i ritonavira, a varijanta UGT1A7 rs17868323 za hiperbilirubinemiju kod bolesnika sa COVID-19 koji se leče ritonavirom. SLCO1B1 rs4149056 je potencijalni marker odgovora na lopinavir, posebno u populaciji Italije. Naši rezultati potvrdili su da se farmakogenomski profil afričke populacije razlikuje od ostatka sveta. Zaključak: Uzimajući u obzir farmakogenomski profil specifičan za populaciju, preventivno testiranje farmakogena značajnih za lekove koji se koriste u lečenju COVID-19 moglo bi doprineti boljem razumevanju interindividualnih razlika u odgovorima na terapiju i poboljšanju ishoda lečenja pacijenata sa COVID-19.
AB  - Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.
PB  - Društvo medicinskih biohemičara Srbije, Beograd i Versita
T2  - Journal of Medical Biochemistry
T1  - Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta
T1  - Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations
EP  - 499
IS  - 4
SP  - 488
VL  - 39
DO  - 10.5937/jomb0-26725
ER  - 

@article{
author = "Stanković, Biljana and Kotur, Nikola and Gašić, Vladimir and Klaassen, Kristel and Ristivojević, Bojan and Stojiljković, Maja and Pavlović, Sonja and Zukić, Branka",
year = "2020",
abstract = "Uvod: Kako ne postoje odobreni terapeutici za lečenje pacijenata sa COVID-19, mogućnost upotrebe postojećih lekova je postala važna. U nedostatku vremena za testiranje farmakogenomskih markera kod pojedinaca, populaciona farmakogenomika bi mogla biti od koristi u predviđanju povećanog rizika za pojavu neželjenih reakcija i neuspeha lečenja kod pacijenata sa COVID-19. Cilj naše studije bio je identifikovanje farmakogena i farmakogenomskih markera povezanih sa lekovima koji se preporučuju za lečenje COVID-19, hlorokin/hidroksihlorokin, azitromicin, lopinavir i ritonavir, u populaciji Srbije i drugim svetskim populacijama. Metode: Podaci o genotipu 143 osobe srpskog porekla dobijeni su iz baze podataka prethodno formirane analizama genoma korišćenjem TruSight One Gene Panel (Illumina). Podaci o genotipu pojedinaca iz različitih svetskih populacija dobijeni su iz Projekta 1000 genoma. Fišerov egzaktni test korišćen je za poređenje učestalosti alela. Rezultati: Identifikovali smo 11 potencijalnih farmakogenomskih markera u 7 farmakogena značajnih za lečenje COVID-19. Na osnovu visoke alterativne učestalosti alela u populaciji Srbije i funkcionalnog efekta varijanti, ABCB1 rs1045642 i rs2032582 mogu biti značajne za smanjeni klirens lekova azitromicina, lopinavira i ritonavira, a varijanta UGT1A7 rs17868323 za hiperbilirubinemiju kod bolesnika sa COVID-19 koji se leče ritonavirom. SLCO1B1 rs4149056 je potencijalni marker odgovora na lopinavir, posebno u populaciji Italije. Naši rezultati potvrdili su da se farmakogenomski profil afričke populacije razlikuje od ostatka sveta. Zaključak: Uzimajući u obzir farmakogenomski profil specifičan za populaciju, preventivno testiranje farmakogena značajnih za lekove koji se koriste u lečenju COVID-19 moglo bi doprineti boljem razumevanju interindividualnih razlika u odgovorima na terapiju i poboljšanju ishoda lečenja pacijenata sa COVID-19., Background: Since there are no certified therapeutics to treat COVID-19 patients, drug repurposing became important. With lack of time to test individual pharmacogenomics markers, population pharmacogenomics could be helpful in predicting a higher risk of developing adverse reactions and treatment failure in COVID-19 patients. Aim of our study was to identify pharmacogenes and pharmacogenomics markers associated with drugs recommended for COVID-19 treatment, chloroquine/hydroxychloroquine, azithromycin, lopinavir and ritonavir, in population of Serbia and other world populations. Methods: Genotype information of 143 individuals of Serbian origin was extracted from database previously obtained using TruSight One Gene Panel (Illumina). Genotype data of individuals from different world populations were extracted from the 1000 Genome Project. Fisher's exact test was used for comparison of allele frequencies. Results: We have identified 11 potential pharmacogenomics markers in 7 pharmacogenes relevant for COVID-19 treatment. Based on high alternative allele frequencies in population and the functional effect of the variants, ABCB1 rs1045642 and rs2032582 could be relevant for reduced clearance of azithromycin, lopinavir and ritonavir drugs and UGT1A7 rs17868323 for hyperbilirubinemia in ritonavir treated COVID-19 patients in Serbian population. SLCO1B1 rs4149056 is a potential marker of lopinavir response, especially in Italian population. Our results confirmed that pharmacogenomics profile of African population is different from the rest of the world. Conclusions: Considering population specific pharmacogenomics landscape, preemptive testing for pharmacogenes relevant for drugs used in COVID-19 treatment could contribute to better understanding of the inconsistency in therapy response and could be applied to improve the outcome of the COVID-19 patients.",
publisher = "Društvo medicinskih biohemičara Srbije, Beograd i Versita",
journal = "Journal of Medical Biochemistry",
title = "Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta, Pharmacogenomics landscape of COVID-19 therapy response in Serbian population and comparison with worldwide populations",
pages = "499-488",
number = "4",
volume = "39",
doi = "10.5937/jomb0-26725"
}

Stanković, B., Kotur, N., Gašić, V., Klaassen, K., Ristivojević, B., Stojiljković, M., Pavlović, S.,& Zukić, B.. (2020). Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta. in Journal of Medical Biochemistry
Društvo medicinskih biohemičara Srbije, Beograd i Versita., 39(4), 488-499.
https://doi.org/10.5937/jomb0-26725

Stanković B, Kotur N, Gašić V, Klaassen K, Ristivojević B, Stojiljković M, Pavlović S, Zukić B. Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta. in Journal of Medical Biochemistry. 2020;39(4):488-499.
doi:10.5937/jomb0-26725 .

Stanković, Biljana, Kotur, Nikola, Gašić, Vladimir, Klaassen, Kristel, Ristivojević, Bojan, Stojiljković, Maja, Pavlović, Sonja, Zukić, Branka, "Farmakogenomski profil odgovora na terapiju za COVID-19 u populaciji Srbije i poređenje sa populacijama širom sveta" in Journal of Medical Biochemistry, 39, no. 4 (2020):488-499,
https://doi.org/10.5937/jomb0-26725 . .

TY  - JOUR
AU  - Pavlović, Sonja
AU  - Kotur, Nikola
AU  - Stanković, Biljana
AU  - Gašić, Vladimir
AU  - Lucafo, Marianna
AU  - Decorti, Giuliana
AU  - Zukić, Branka
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1408
AB  - Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Current Drug Metabolism
T1  - Clinical Application of Thiopurine Pharmacogenomics in Pediatrics
EP  - 62
IS  - 1
SP  - 53
VL  - 21
DO  - 10.2174/1389200221666200303113456
ER  - 

@article{
author = "Pavlović, Sonja and Kotur, Nikola and Stanković, Biljana and Gašić, Vladimir and Lucafo, Marianna and Decorti, Giuliana and Zukić, Branka",
year = "2020",
abstract = "Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Pharmacogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment protocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in posttransplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lymphoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Current Drug Metabolism",
title = "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics",
pages = "62-53",
number = "1",
volume = "21",
doi = "10.2174/1389200221666200303113456"
}

Pavlović, S., Kotur, N., Stanković, B., Gašić, V., Lucafo, M., Decorti, G.,& Zukić, B.. (2020). Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism
Bentham Science Publ Ltd, Sharjah., 21(1), 53-62.
https://doi.org/10.2174/1389200221666200303113456

Pavlović S, Kotur N, Stanković B, Gašić V, Lucafo M, Decorti G, Zukić B. Clinical Application of Thiopurine Pharmacogenomics in Pediatrics. in Current Drug Metabolism. 2020;21(1):53-62.
doi:10.2174/1389200221666200303113456 .

Pavlović, Sonja, Kotur, Nikola, Stanković, Biljana, Gašić, Vladimir, Lucafo, Marianna, Decorti, Giuliana, Zukić, Branka, "Clinical Application of Thiopurine Pharmacogenomics in Pediatrics" in Current Drug Metabolism, 21, no. 1 (2020):53-62,
https://doi.org/10.2174/1389200221666200303113456 . .

TY  - JOUR
AU  - Doknić, Mirjana
AU  - Gašić, Vladimir
AU  - Stojanović, Marko
AU  - Pavlović, Sonja
AU  - Marinković, Snežana
AU  - Miljić, Dragana
AU  - Pekić, Sandra
AU  - Manojlović-Gacić, Emilija
AU  - Damjanović, Dusan
AU  - Soldatović, Ivan
AU  - Petakov, Milan
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1404
AB  - Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.
PB  - Springer, New York
T2  - Pituitary
T1  - Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood
EP  - 408
IS  - 4
SP  - 400
VL  - 23
DO  - 10.1007/s11102-020-01049-9
ER  - 

@article{
author = "Doknić, Mirjana and Gašić, Vladimir and Stojanović, Marko and Pavlović, Sonja and Marinković, Snežana and Miljić, Dragana and Pekić, Sandra and Manojlović-Gacić, Emilija and Damjanović, Dusan and Soldatović, Ivan and Petakov, Milan",
year = "2020",
abstract = "Twenty years after the first description of combined hypopituitarism (CPHD) caused by PROP1 mutations, the phenotype of affected subjects is still challenging for clinicians. These patients suffer from pituitary hormone deficits ranging from IGHD to panhypopituitarism. ACTH deficiency usually develops later in life. Pituitary size is variable. PROP1 mutation is the most frequent in familial congenital hypopituitarism (CH). Reports on initiation of hormonal replacement including growth hormone (GH) in adults with CH are scarce. We identified 5 adult siblings with CPHD due to PROP1 mutation (301-302delAG), aged 36-51 years (4 females), never treated for hormone deficiencies. They presented with short stature (SD from - 3.7 to - 4.7), infantile sexual characteristic, moderate abdominal obesity and low bone mineral density in 3 of them. Complete hypopituituitarism was confirmed in three siblings, while two remaining demonstrated GH, TSH, FSH and LH deficiencies. Required hormonal replacement including rhGH was initiated in all patients. After several months necessity for hydrocortisone replacement developed in all patients. After 2 years of continual replacement therapy, BMD and body composition (measured by DXA-dual X-ray absorptiometry) improved in all subjects, most prominently in two younger females and the male sibling. Besides rhGH therapy, these three patients have received sex hormones contributing to the favorable effect. The male sibling was diagnosed with brain glioblastoma two years following complete hormonal replacement. This report provides important experience regarding hormonal replacement, particularly rhGH treatment, in adults with long-term untreated CH. Beneficial effect of such therapy are widely acknowledged, yet these subjects could be susceptible to certain risks of hormonal treatment initiated in adulthood. Careful and continual clinical follow-up is thus strongly advised.",
publisher = "Springer, New York",
journal = "Pituitary",
title = "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood",
pages = "408-400",
number = "4",
volume = "23",
doi = "10.1007/s11102-020-01049-9"
}

Doknić, M., Gašić, V., Stojanović, M., Pavlović, S., Marinković, S., Miljić, D., Pekić, S., Manojlović-Gacić, E., Damjanović, D., Soldatović, I.,& Petakov, M.. (2020). Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary
Springer, New York., 23(4), 400-408.
https://doi.org/10.1007/s11102-020-01049-9

Doknić M, Gašić V, Stojanović M, Pavlović S, Marinković S, Miljić D, Pekić S, Manojlović-Gacić E, Damjanović D, Soldatović I, Petakov M. Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood. in Pituitary. 2020;23(4):400-408.
doi:10.1007/s11102-020-01049-9 .

Doknić, Mirjana, Gašić, Vladimir, Stojanović, Marko, Pavlović, Sonja, Marinković, Snežana, Miljić, Dragana, Pekić, Sandra, Manojlović-Gacić, Emilija, Damjanović, Dusan, Soldatović, Ivan, Petakov, Milan, "Hypopituitarism in five PROP1 mutation siblings: long-lasting natural course and the effects of growth hormone replacement introduction in middle adulthood" in Pituitary, 23, no. 4 (2020):400-408,
https://doi.org/10.1007/s11102-020-01049-9 . .