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

Abstract

The biological characterization of childhood acute myeloid leu kemia (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 (2000e2015) were as sessed 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, CBFb-MYH11, and PML-RARa) 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; O2e10 years old and $11 years old) and the nonrandom association be tween type I/II mutations. Lower white blood cell count (#50 109 /L) was associated with RUNX1-RUNX1T1, whereas higher WBC with CBFb-MYH11 ( p !0.05). Cumula tive pOS in 5 years was 37.7 2.8% for total AMLs and 59.8 6.2% for APL ( p 5 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 in dependent prognostic factor. Conclusions. Identification of genetic subgroups contributes to the molecular epidemi ology and biology of AML worldwide, reflecting the profile of pediatric AML cases in Brazil.