AUTHOR=Molina Garay Carolina , Carrillo Sánchez Karol , Flores Lagunes Luis Leonardo , Jiménez Olivares Marco , Muñoz Rivas Anallely , Villegas Torres Beatríz Eugenia , Flores Aguilar Hilario , Núñez Enríquez Juan Carlos , Jiménez Hernández Elva , Bekker Méndez Vilma Carolina , Torres Nava José Refugio , Flores Lujano Janet , Martín Trejo Jorge Alfonso , Mata Rocha Minerva , Medina Sansón Aurora , Espinoza Hernández Laura Eugenia , Peñaloza Gonzalez José Gabriel , Espinosa Elizondo Rosa Martha , Flores Villegas Luz Victoria , Amador Sanchez Raquel , Pérez Saldívar Maria Luisa , Sepúlveda Robles Omar Alejandro , Rosas Vargas Haydeé , Rangel López Angélica , Domínguez López María Lilia , García Latorre Ethel Awilda , Reyes Maldonado Elba , Galindo Delgado Patricia , Mejía Aranguré Juan Manuel , Alaez Verson Carmen 

TITLE=Profiling FLT3 Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients: Impact on Overall Survival

JOURNAL=Frontiers in Pediatrics

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00586

DOI=10.3389/fped.2020.00586

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The <italic>FLT3</italic> gene participates in hematopoietic stem cell proliferation. <italic>FLT3</italic> mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, <italic>FLT3</italic> mutational profile, and their clinical impact have not been evaluated.</p><p><bold>Aim of the study:</bold> This study aimed to identify the profile of <italic>FLT3</italic> mutations in pediatric patients with <italic>de novo</italic> AML and to assess their possible influence on overall survival (OS) and other clinical features.</p><p><bold>Methods:</bold> Massive parallel target sequencing of <italic>FLT3</italic> was performed in 80 patients.</p><p><bold>Results:</bold><italic>FLT3</italic> mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower in <italic>FLT3</italic><sup>POS</sup> cases than in <italic>FLT3</italic><sup>NEG</sup> (<italic>p</italic> = 0.03). The average OS for <italic>FLT3</italic><sup>POS</sup> was 1.2 vs. 2.2 years in <italic>FLT3</italic><sup>NEG</sup>. 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 &gt; 0.4) or type of mutation. The negative effect of <italic>FLT3</italic> mutations was also observed in patients with acute promyelocytic leukemia (APL).</p><p><bold>Conclusions:</bold><italic>FLT3</italic> mutational profile is described in Mexican pediatric AML patients for the first time. Mutated <italic>FLT3</italic> negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in the <italic>FLT3</italic><sup>POS</sup> pediatric patients needs to be assessed in clinical trials. <italic>FLT3</italic> testing may contribute to better risk stratification in our pediatric AML patients.</p>