Clinicopathological and global methylation profiling of acute myeloid leukemia with mutations in NPM1 and clonal hematopoiesis-related genes.

Recent studies suggest that nucleophosmin 1 (NPM1)-mutated acute myeloid leukemia (NPM1-AML) often arises from clonal hematopoiesis (CH) involving mutations in DTA genes (DNMT3A, TET2, ASXL1), which can persist during remission. This research evaluates the clinical implications of molecular profiling of CH-related DTA genes in NPM1-AML by comparing clinical features, treatment outcomes, and methylation patterns with those of NPM1-AML lacking DTA mutations. Findings show NPM1-AML with DTA mutations exhibited higher WBC/peripheral blood blast counts, a lower incidence of extramedullary disease, more frequent IDH2 but less FLT3-TKD mutations. However, no significant differences in clinical characteristics such as age, treatment response, or disease outcome between the groups were seen. Additionally, despite variations in methylation profiles based on disease status, no distinct differences between DTA-positive and negative groups were observed. Notably, three probes, including one linked to the FAM65B promoter, effectively differentiated disease states, highlighting the potential role of FAM65B in leukemogenesis and patient survival.