Clinicopathological and global methylation profiling of acute myeloid leukemia with mutations in <i>NPM1</i> and clonal hematopoiesis-related genes

Recent studies suggest that nucleophosmin 1 (<i>NPM1</i>)-mutated acute myeloid leukemia (<i>NPM1</i>-AML) often arises from clonal hematopoiesis (CH) involving mutations in <i>DTA</i> genes (<i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>), which can persist during remission. This research evaluates the clinical implications of molecular profiling of CH-related <i>DTA</i> genes in <i>NPM1</i>-AML by comparing clinical features, treatment outcomes, and methylation patterns with those of <i>NPM1</i>-AML lacking <i>DTA</i> mutations. Findings show <i>NPM1</i>-AML with <i>DTA</i> mutations exhibited higher WBC/peripheral blood blast counts, a lower incidence of extramedullary disease, more frequent <i>IDH2</i> but less <i>FLT3</i>-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 <i>DTA</i>-positive and negative groups were observed. Notably, three probes, including one linked to the <i>FAM65B</i> promoter, effectively differentiated disease states, highlighting the potential role of <i>FAM65B</i> in leukemogenesis and patient survival.