Abstract
Background: Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The FLT3 gene participates in hematopoietic stem cell proliferation. FLT3 mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated.Aim of the study: This study aimed to identify the profile of FLT3 mutations in pediatric patients with de novo AML and to assess their possible influence on overall survival (OS) and other clinical features.Methods: Massive parallel target sequencing of FLT3 was performed in 80 patients.Results: FLT3 mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in FLT3POS cases than in FLT3NEG (p = 0.03). The average OS for FLT3POS was 1.2 vs. 2.2 years in FLT3NEG. There were no significant differences in the children's sex, age, percentage of blasts in bone marrow aspirate, or white blood cell count in peripheral blood at diagnosis between both groups. No differences were identified stratifying by the mutational load (high > 0.4) or type of mutation. The negative effect of FLT3 mutations was also observed in patients with acute promyelocytic leukemia (APL).Conclusions: FLT3 mutational profile is described in Mexican pediatric AML patients for the first time. Mutated FLT3 negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the FLT3POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients.
Highlights
Genomic investigations of acute myeloid leukemia (AML) have demonstrated that several genes are recurrently mutated, leading to the identification of new biomarkers
The bone marrow samples analyzed in the present study were obtained at the time of the diagnosis, before treatment initiation, and submitted to the Mexican InterInstitutional Group for Identifying Childhood Leukemia Causes in Mexico City
Our results suggest that both FLT3-TKD and Internal tandem duplications (ITDs) mutations have a similar negative effect on overall survival (OS) in pediatric patients
Summary
Genomic investigations of acute myeloid leukemia (AML) have demonstrated that several genes are recurrently mutated, leading to the identification of new biomarkers. FLT3 gene mutations are among the most frequently observed in AML, which occurs in approximately onethird of patients with de novo AML. They have been associated with the clinical prognosis, treatment response, and survival of patients [3]. Internal tandem duplications (ITDs) affect the juxtamembrane (JM) domain or tyrosine kinase domain 1 (TKD1) of the FLT3 receptor and point mutation preset in the TKD2 [4]. Both types of mutations promote ligand-independent auto-phosphorylation and constitutive activation of the receptor. In Mexican pediatric AML patients, FLT3 mutational profile, and their clinical impact have not been evaluated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
