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Leuk Res ; 141: 107500, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636413

RESUMO

Mutations in spliceosome genes (SRSF2, SF3B1, U2AF1, ZRSR2) correlate with inferior outcomes in patients treated with intensive chemotherapy for Acute Myeloid Leukemia. However, their prognostic impact in patients treated with less intensive protocols is not well known. This study aimed to evaluate the impact of Spliceosome mutations in patients treated with Venetoclax and Azacitidine for newly diagnosed AML. 117 patients treated in 3 different hospitals were included in the analysis. 34 harbored a mutation in at least one of the spliceosome genes (splice-mut cohort). K/NRAS mutations were more frequent in the splice-mut cohort (47% vs 19%, p=0.0022). Response rates did not differ between splice-mut and splice-wt cohorts. With a median follow-up of 15 months, splice mutations were associated with a lower 18-month LFS (p=0.0045). When analyzing splice mutations separately, we found SRSF2 mutations to be associated with poorer outcomes (p=0.034 and p=0.037 for OS and LFS respectively). This negative prognostic impact remained true in our multivariate analysis. We believe this finding should warrant further studies aimed at overcoming this negative impact.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Mutação , Fatores de Processamento de Serina-Arginina , Humanos , Fatores de Processamento de Serina-Arginina/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Idoso , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Azacitidina/uso terapêutico , Azacitidina/administração & dosagem , Adulto Jovem , Spliceossomos/genética , Sulfonamidas
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