Molecular Characterization of Pediatric Acute Myeloid Leukemia: Results of a Multicentric Study in Brazil.

Autor: Andrade FG; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Noronha EP; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Brisson GD; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Dos Santos Vicente Bueno F; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Cezar IS; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Terra-Granado E; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Thuler LCS; Clinical Research Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil., Pombo-de-Oliveira MS; Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: mpombo@inca.gov.br.
Jazyk: angličtina
Zdroj: Archives of medical research [Arch Med Res] 2016 Nov; Vol. 47 (8), pp. 656-667.
DOI: 10.1016/j.arcmed.2016.11.015
Abstrakt: Background and Aims: The biological characterization of childhood acute myeloid leukemia (c-AML) is an important outcome predictor. In Brazil, very little is known about the frequency of AML subgroups, although c-AML accounts for about 18% of leukemias. We carried out this study to investigate the contribution of type I and II gene mutations in the probability of overall survival (pOS) of c-AML in Brazil.
Methods: Seven hundred and three de novo pediatric AML cases (2000-2015) were assessed throughout a multicentric network study. Mutations in hotspot regions of FLT3, NRAS, KRAS, PTPN11, and c-KIT genes were analyzed as well as fusion genes (RUNX1-RUNX1T1, MLL/KMT2A-r, CBFβ-MYH11, and PML-RARα) associated with AML. Patients were treated out of the clinical trial although following the BFM-AML2004 protocol. Acute promyelocytic leukemia (APL) was treated differently. AML with Down syndrome was excluded.
Results: There were significant differences in gene mutations among age ranges (≤2 years-old; >2-10 years old and ≥11 years old) and the nonrandom association between type I/II mutations. Lower white blood cell count (≤50 × 10 9 /L) was associated with RUNX1-RUNX1T1, whereas higher WBC with CBFβ-MYH11 (p <0.05). Cumulative pOS in 5 years was 37.7 ± 2.8% for total AMLs and 59.8 ± 6.2% for APL (p = 0.03). pOS differences were observed between Brazilian regions. The South-Southeast regions had a better 5-year pOS, whereas the Midwest region presented the poorest pOS (23.7 ± 4.9%). PTPN11 mutations conferred an adverse prognosis as an independent prognostic factor.
Conclusions: Identification of genetic subgroups contributes to the molecular epidemiology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil.
(Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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