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


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 FLT3 POS cases than in FLT3 NEG (p = 0.03). The average OS for FLT3 POS was 1.2 vs. 2.2 years in FLT3 NEG. 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 FLT3 POS pediatric patients needs to be assessed in clinical trials. FLT3 testing may contribute to better risk stratification in our pediatric AML patients.

SUBMITTER: Molina Garay C 

PROVIDER: S-EPMC7525023 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Profiling <i>FLT3</i> Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients: Impact on Overall Survival.

Molina Garay Carolina C   Carrillo Sánchez Karol K   Flores Lagunes Luis Leonardo LL   Jiménez Olivares Marco M   Muñoz Rivas Anallely A   Villegas Torres Beatríz Eugenia BE   Flores Aguilar Hilario H   Núñez Enríquez Juan Carlos JC   Jiménez Hernández Elva E   Bekker Méndez Vilma Carolina VC   Torres Nava José Refugio JR   Flores Lujano Janet J   Martín Trejo Jorge Alfonso JA   Mata Rocha Minerva M   Medina Sansón Aurora A   Espinoza Hernández Laura Eugenia LE   Peñaloza Gonzalez José Gabriel JG   Espinosa Elizondo Rosa Martha RM   Flores Villegas Luz Victoria LV   Amador Sanchez Raquel R   Pérez Saldívar Maria Luisa ML   Sepúlveda Robles Omar Alejandro OA   Rosas Vargas Haydeé H   Rangel López Angélica A   Domínguez López María Lilia ML   García Latorre Ethel Awilda EA   Reyes Maldonado Elba E   Galindo Delgado Patricia P   Mejía Aranguré Juan Manuel JM   Alaez Verson Carmen C  

Frontiers in pediatrics 20200916


<b>Background:</b> Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. The <i>FLT3</i> gene participates in hematopoietic stem cell proliferation. <i>FLT3</i> mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients, <i>FLT3</i> mutational profile, and their clinical impact have not been evaluated. <b>Aim of the study:</b> This study aimed to identify the profile of <i>FLT3</i> mutations in pediatric patients with <i>de novo</i> AML an  ...[more]

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