Profilingflt3mutations In Mexican Acute Myeloid Leukemia Pediatric Patients: Impact On Overall Survival

FRONTIERS IN PEDIATRICS(2020)

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摘要
Background:Acute myeloid leukemia (AML) is the second most frequent leukemia in childhood. TheFLT3gene participates in hematopoietic stem cell proliferation.FLT3mutations are recurrent in AML and influence prognosis. In Mexican pediatric AML patients,FLT3mutational profile, and their clinical impact have not been evaluated. Aim of the study:This study aimed to identify the profile ofFLT3mutations in pediatric patients withde novoAML and to assess their possible influence on overall survival (OS) and other clinical features. Methods:Massive parallel target sequencing ofFLT3was performed in 80 patients. Results:FLT3mutations [internal tandem duplication (ITD) or tyrosine kinase domain (TKD)] were identified in 24% of them. OS was significantly lower inFLT3(POS)cases than inFLT3(NEG)(p= 0.03). The average OS forFLT3(POS)was 1.2 vs. 2.2 years inFLT3(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 ofFLT3mutations was also observed in patients with acute promyelocytic leukemia (APL). Conclusions:FLT3mutational profile is described in Mexican pediatric AML patients for the first time. MutatedFLT3negatively impacts the outcome of AML patients, even considering the APL group. The clinical benefit from treatment with tyrosine kinase inhibitors in theFLT3(POS)pediatric patients needs to be assessed in clinical trials.FLT3testing may contribute to better risk stratification in our pediatric AML patients.
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关键词
FLT3, pediatric, Mexican, AML, survival, risk-stratification
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