Clinical and biological implications of mutational spectrum in acute myeloid leukemia of FAB subtypes M4 and M5

The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French–American–British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.