TY - JOUR
T1 - Profiling FLT3 Mutations in Mexican Acute Myeloid Leukemia Pediatric Patients
T2 - Impact on Overall Survival
AU - Molina Garay, Carolina
AU - Carrillo Sánchez, Karol
AU - Flores Lagunes, Luis Leonardo
AU - Jiménez Olivares, Marco
AU - Muñoz Rivas, Anallely
AU - Villegas Torres, Beatríz Eugenia
AU - Flores Aguilar, Hilario
AU - Núñez Enríquez, Juan Carlos
AU - Jiménez Hernández, Elva
AU - Bekker Méndez, Vilma Carolina
AU - Torres Nava, José Refugio
AU - Flores Lujano, Janet
AU - Martín Trejo, Jorge Alfonso
AU - Mata Rocha, Minerva
AU - Medina Sansón, Aurora
AU - Espinoza Hernández, Laura Eugenia
AU - Peñaloza Gonzalez, José Gabriel
AU - Espinosa Elizondo, Rosa Martha
AU - Flores Villegas, Luz Victoria
AU - Amador Sanchez, Raquel
AU - Pérez Saldívar, Maria Luisa
AU - Sepúlveda Robles, Omar Alejandro
AU - Rosas Vargas, Haydeé
AU - Rangel López, Angélica
AU - Domínguez López, María Lilia
AU - García Latorre, Ethel Awilda
AU - Reyes Maldonado, Elba
AU - Galindo Delgado, Patricia
AU - Mejía Aranguré, Juan Manuel
AU - Alaez Verson, Carmen
N1 - Publisher Copyright:
© Copyright © 2020 Molina Garay, Carrillo Sánchez, Flores Lagunes, Jiménez Olivares, Muñoz Rivas, Villegas Torres, Flores Aguilar, Núñez Enríquez, Jiménez Hernández, Bekker Méndez, Torres Nava, Flores Lujano, Martín Trejo, Mata Rocha, Medina Sansón, Espinoza Hernández, Peñaloza Gonzalez, Espinosa Elizondo, Flores Villegas, Amador Sanchez, Pérez Saldívar, Sepúlveda Robles, Rosas Vargas, Rangel López, Domínguez López, García Latorre, Reyes Maldonado, Galindo Delgado, Mejía Aranguré and Alaez Verson.
PY - 2020/9/16
Y1 - 2020/9/16
N2 - 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.
AB - 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.
KW - AML
KW - FLT3
KW - Mexican
KW - pediatric
KW - risk-stratification
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85091918521&partnerID=8YFLogxK
U2 - 10.3389/fped.2020.00586
DO - 10.3389/fped.2020.00586
M3 - Artículo
AN - SCOPUS:85091918521
SN - 2296-2360
VL - 8
JO - Frontiers in Pediatrics
JF - Frontiers in Pediatrics
M1 - 586
ER -