Complex molecular genetic abnormalities involving three or more genetic mutations are important prognostic factors for acute myeloid leukemia

We conducted a comprehensive analysis of 28 recurrently mutated genes in acute myeloid leukemia (AML) in 271 patients with de novo AML. Co-mutations were frequently detected in the intermediate cytogenetic risk group, at an average of 2.76 co-mutations per patient. When assessing the prognostic impact of these co-mutations in the intermediate cytogenetic risk group, overall survival (OS) was found to be significantly shorter ( P =0.0006) and cumulative incidence of relapse (CIR) significantly higher ( P =0.0052) in patients with complex molecular genetic abnormalities (CMGAs) involving three or more mutations. This trend was marked even among patients aged ⩽65 years who were also FLT3 -ITD ( FMS-like tyrosine kinase 3 internal tandem duplications)-negative (OS: P =0.0010; CIR: P =0.1800). Moreover, the multivariate analysis revealed that CMGA positivity was an independent prognostic factor associated with OS ( P =0.0007). In stratification based on FLT3 -ITD and CEBPA status and ‘simplified analysis of co-mutations’ using seven genes that featured frequently in CMGAs, CMGA positivity retained its prognostic value in transplantation-aged patients of the intermediate cytogenetic risk group (OS: P =0.0002. CIR: P