Format

Send to

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

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

Author information

1
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
2
Clinical Research Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
3
Pediatric Hematology-Oncology Program, Research Center, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. Electronic address: mpombo@inca.gov.br.

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

PMID:
28476193
DOI:
10.1016/j.arcmed.2016.11.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center