Expression levels of BCL2, BAX and MDR1 as pharmacotranscriptomic and prognostic markers of prognosis in acute myeloid leukemia
Аутори
Gašić, VladimirPravdić, Zlatko
Suvajdžić Vuković, Nada
Marjanović, Irena
Karan-Đurašević, Teodora
Pavlović, Sonja
Tošić, Nataša
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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=0.01...8), 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.
Кључне речи:
AML / BCL2 / BAX / MDR1 / prognosisИзвор:
Genetics & Applications, 2023, 7Издавач:
- Sarajevo : Institute for Genetic Engineering and Biotechnology, University of Sarajevo
Напомена:
- Book of abstracts: International Conference of Biochemists and Molecular Biologists in Bosnia and Herzegovina - ABMBBIH May, 2023
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 .