Genotypic and clinical heterogeneity within NCCN favorable-risk acute myeloid leukemia. (February 2018) - Strickland, Stephen A.
Highlights: This study identified differences in the characteristics of favorable-risk AML. AML with normal karyotype and NPM1 mutations is distinct in age and karyotype. These patients have worse overall survival than other types of favorable-risk AML. Further study is needed to determine if different treatment approaches are warranted. Abstract: The National Comprehensive Cancer Network (NCCN) defines the following types of acute myeloid leukemia (AML) as favorable-risk: acute promyelocytic leukemia with t(15;17) (APL); AML with core-binding factor (CBF) rearrangements, including t(8;21) and inv(16) or t(16;16) without mutations in KIT (CBF- KIT wt ); and AML with normal cytogenetics and mutations in NPM1 ( NPM1 mut ); or biallelic mutations in CEBPA ( CEBPA mut/mut ), without FLT3-ITD. Although these AMLs are categorized as favorable risk by NCCN, clinical experience suggests that there are differences in clinical outcome amongst these cytogenetically and molecularly distinct leukemias. This study compared clinical and genotypic characteristics of 60 patients with favorable-risk AML, excluding APL, and demonstrated significant differences between them. Patients with NPM1 mut AML were significantly older than those in the other groups. Targeted next-generation sequencing on DNA from peripheral blood or bone marrow revealed significantly more mutations in NPM1 mut AML than the other favorable-risk diseases, especially in genes related to DNA splicing and methylation. CEBPA mut/mut AMLs exhibited more mutations in transcription-related genes. Patients with NPM1 mut AML and CEBPA mut/mut AML show significantly reduced overall survival in comparison with CBF- KIT wt AML. These findings emphasize that favorable-risk AML patients have divergent outcomes and that differences in clinical and genotypic characteristics should be considered in their evaluation and management.