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

Arch Med Res. 2016 Nov;47(8):656-667. doi: 10.1016/j.arcmed.2016.11.015.

Abstract

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 × 109/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.

Keywords: Brazilian AML; Molecular markers; Pediatric AML; Prognosis; Type I/II mutations.

Publication types

  • Multicenter Study

MeSH terms

  • Brazil
  • Child
  • Child, Preschool
  • Female
  • Gene Expression Profiling
  • Genetic Association Studies
  • Humans
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Mutation
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Prognosis
  • Survival Analysis

Substances

  • Oncogene Proteins, Fusion