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ORIGINAL RESEARCH article

Front. Pediatr.
Sec. Pediatric Hematology and Hematological Malignancies
Volume 12 - 2024 | doi: 10.3389/fped.2024.1505060

Prevalence of FLT3 gene mutation and its expression in Brazilian pediatric B-ALL patients: Clinical Implications

Provisionally accepted
ESTEFANIA BIOJONE ESTEFANIA BIOJONE 1*Bruna Cândido Guido Bruna Cândido Guido 2Larissa Lemos Mendanha Cavalcante Larissa Lemos Mendanha Cavalcante 2Agenor de Castro Moreira dos Santos Junior Agenor de Castro Moreira dos Santos Junior 2Robéria Mendonça Pontes Robéria Mendonça Pontes 2Felipe Magalhães Furtado Felipe Magalhães Furtado 3,4José Carlos Córdoba José Carlos Córdoba 3Isis Maria Quezado Magalhães Isis Maria Quezado Magalhães 1Diêgo Madureira De Oliveira Diêgo Madureira De Oliveira 5*Ricardo Camargo Ricardo Camargo 2*
  • 1 Oncology and Hematology Division, Children’s Hospital of Brasilia, Brasilia, Brazil
  • 2 Laboratory of Translational Research, Children’s Hospital of Brasilia, Brasilia, Brazil
  • 3 Laboratory of Translational Research, Oncology and Hematology Division, Children’s Hospital of Brasilia, Brasilia, Brazil
  • 4 Sabin Diagnóstico e Saúde, Brasilia, Brazil
  • 5 Multidisciplinary Health Laboratory, Faculty of Ceilândia, University of Brasilia, Brasilia, Distrito Federal, Brazil

The final, formatted version of the article will be published soon.

    There is consistent evidence that FLT3 may be a driver gene in B-ALL and that selected cases may benefit from the use of FLT3 inhibitors. Our study was conducted to evaluate the frequency and types of FLT3 mutations in pediatric patients with B-ALL, the relative expression of this gene, and their influence on clinical evolution. We evaluated 156 children with B-ALL treated between July 2018 and September 2023. Screening for FLT3 mutations was performed using RFLP and fragment analysis, while FLT3 expression was assessed by qPCR. FLT3-TKD and/or FLT3-JM-INDEL mutations were found in 8 patients (5.1%). We did not identify any ITD-type mutations. None of the patients with identified FLT3 mutations presented recurrent rearrangements in B-ALL or alterations in the IKZF1, PAX5, or ERG genes, suggesting that FLT3 mutation may serve as the driving mechanism for leukemia in these cases. Two (2/8) patients with FLT3 mutations experienced disease relapse. Although we did not observe FLT3 overexpression among patients with FLT3 mutations, FLT3 expression levels were higher in these patients compared to WT patients. Four FLT3-WT patients presented FLT3 overexpression, defined as RQ > 10. FLT3 mutations or overexpression were not associated with relapse or survival rates. Our findings do not support the inclusion of FLT3 as a routine marker in the risk stratification of B-ALL patients; nevertheless, FLT3 alterations may be relevant for guiding personalized treatment approaches in specific clinical contexts.

    Keywords: Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, precision medicine, Molecular Biology, Tumor biomarkers, Child Health

    Received: 02 Oct 2024; Accepted: 19 Nov 2024.

    Copyright: © 2024 BIOJONE, Guido, Cavalcante, Santos Junior, Pontes, Furtado, Córdoba, Magalhães, De Oliveira and Camargo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    ESTEFANIA BIOJONE, Oncology and Hematology Division, Children’s Hospital of Brasilia, Brasilia, Brazil
    Diêgo Madureira De Oliveira, Multidisciplinary Health Laboratory, Faculty of Ceilândia, University of Brasilia, Brasilia, 70910-900, Distrito Federal, Brazil
    Ricardo Camargo, Laboratory of Translational Research, Children’s Hospital of Brasilia, Brasilia, Brazil

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