Myeloid sarcoma with NPM1 mutation may be clinically and genetically distinct from AML with NPM1 mutation: a study from the Bone Marrow Pathology Group.

Myeloid sarcoma (MS) is currently considered equivalent to de novo acute myeloid leukemia (AML); however, the relationship between these entities is poorly understood. This retrospective multi-institutional cohort study compared 43 MS with NPM1 mutation to 106 AML with NPM1 mutation. Compared to AML, MS had more frequent cytogenetic abnormalities including complex karyotype ( p  = .009 and p  = .007, respectively) and was enriched in mutations of genes involved in histone modification, including ASXL1 ( p  = .007 and p  = .008, respectively). AML harbored a higher average number of gene mutations ( p  = .002) including more frequent PTPN11 mutations ( p  < .001) and mutations of DNA-methylating genes including DNMT3A and IDH1 (both p  < .001). MS had significantly shorter overall survival (OS) than AML (median OS: 44.9 vs. 93.2 months, respectively, p  = .037). MS with NPM1 mutation has a unique genetic landscape, and poorer OS, compared to AML with NPM1 mutation.