Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia
2016
Преузимање 🢃
Аутори
Janković, SrdjaMarjanović, Irena
Tošić, Nataša
Kotur, Nikola
Dokmanović, Lidija
Skorić, Dejan
Krstovski, Nada
Lazić, Jelena
Rodić, Predrag
Pavlović, Sonja
Janić, Dragana
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and... sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context.
Кључне речи:
Wilms tumor (WT)1 / leukemia / childrenИзвор:
Genetika-Belgrade, 2016, 48, 1, 409-421Издавач:
- Društvo genetičara Srbije, Beograd
Финансирање / пројекти:
- Ретке болести: молекуларна патофизиологија, дијагностички и терапијски модалитети и социјални, етички и правни аспекти (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41004)
DOI: 10.2298/GENSR1601409J
ISSN: 0534-0012
WoS: 000376744800033
Scopus: 2-s2.0-84971325208
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Janković, Srdja AU - Marjanović, Irena AU - Tošić, Nataša AU - Kotur, Nikola AU - Dokmanović, Lidija AU - Skorić, Dejan AU - Krstovski, Nada AU - Lazić, Jelena AU - Rodić, Predrag AU - Pavlović, Sonja AU - Janić, Dragana PY - 2016 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/946 AB - Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context. PB - Društvo genetičara Srbije, Beograd T2 - Genetika-Belgrade T1 - Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia EP - 421 IS - 1 SP - 409 VL - 48 DO - 10.2298/GENSR1601409J ER -
@article{ author = "Janković, Srdja and Marjanović, Irena and Tošić, Nataša and Kotur, Nikola and Dokmanović, Lidija and Skorić, Dejan and Krstovski, Nada and Lazić, Jelena and Rodić, Predrag and Pavlović, Sonja and Janić, Dragana", year = "2016", abstract = "Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context.", publisher = "Društvo genetičara Srbije, Beograd", journal = "Genetika-Belgrade", title = "Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia", pages = "421-409", number = "1", volume = "48", doi = "10.2298/GENSR1601409J" }
Janković, S., Marjanović, I., Tošić, N., Kotur, N., Dokmanović, L., Skorić, D., Krstovski, N., Lazić, J., Rodić, P., Pavlović, S.,& Janić, D.. (2016). Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia. in Genetika-Belgrade Društvo genetičara Srbije, Beograd., 48(1), 409-421. https://doi.org/10.2298/GENSR1601409J
Janković S, Marjanović I, Tošić N, Kotur N, Dokmanović L, Skorić D, Krstovski N, Lazić J, Rodić P, Pavlović S, Janić D. Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia. in Genetika-Belgrade. 2016;48(1):409-421. doi:10.2298/GENSR1601409J .
Janković, Srdja, Marjanović, Irena, Tošić, Nataša, Kotur, Nikola, Dokmanović, Lidija, Skorić, Dejan, Krstovski, Nada, Lazić, Jelena, Rodić, Predrag, Pavlović, Sonja, Janić, Dragana, "Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia" in Genetika-Belgrade, 48, no. 1 (2016):409-421, https://doi.org/10.2298/GENSR1601409J . .