NPM1-mutated AML-MRC diagnosed on the basis of history of MDS or MDS/MPN frequently harbours secondary-type mutations and confers inferior outcome compared to AML with mutated NPM1.

BACKGROUND:Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a prognostically diverse disease. Owing to its favourable prognosis, AML-MRC with mutated NPM1 (NPM1MUT) diagnosed on the basis of multi-lineage dysplasia has been reclassified into "AML with mutated NPM1". However, it remains unclear if NPM1MUT AML with antecedent MDS or MDS/MPN (AML-MRC-H) should also be reclassified into this subentity. The mutational landscape of NPM1MUT AML-MRC-H remains poorly defined. METHODS:The clinicopathological features, molecular profiles and outcomes of 241 AML-MRC-H and 332 normal karyotype (NK)-AML with mutated NPM1 patients were retrospectively analyzed. Fisher's exact test, chi-square test and Wilcoxon rank-sum test were used to compare clinicopathological and molecular features. Overall survival and event-free survival were compared using the log-rank test. Multivariable survival analysis was performed using Cox proportional hazards regression. RESULTS:33 (14%) AML-MRC-H patients had an NPM1 mutation. By NGS, NPM1MUT AML-MRC-H patients had a significantly higher frequency of secondary-type mutations in U2AF1 and ASXL1 compared to NK-AML with mutated NPM1. NPM1MUT AML-MRC-H was significantly associated with inferior outcomes compared to NK-AML with mutated NPM1. Bone marrow transplantation had a favourable prognostic impact in NPM1MUT AML-MRC-H. CONCLUSIONS:NPM1MUT AML-MRC-H has inferior prognosis compared to NK-AML with mutated NPM1, likely due to the higher frequency of secondary-type mutations, and thus should still be included in the high-risk subentity of AML-MRC. NPM1MUT AML-MRC patients may benefit from bone marrow transplantation.