Differential impact of IDH1/2 mutations on outcome in adult acute myeloid leukemia patients.

Mutations in Isocitrate Dehydrogenase-1 (IDH1) and IDH2 lead to abnormal histone hypermethylation and DNA modifications, disrupting cell differentiation, yet the clinical and prognostic significance of these mutations in primary acute myeloid leukemia (AML) remains debated. This study retrospectively analyzed 181 newly diagnosed AML patients, categorizing them into IDH1mut, IDH2mut, and IDHwt groups to compare clinical features, mutational profiles, and outcomes. IDH1 and IDH2 mutations were detected in 7.7 % (14/181) and 11.6 % (21/181) of cases, respectively. Patients with IDH mutations were older, had higher platelet counts, elevated WT1 mRNA expression, and lower white blood cell counts compared to IDHwt patients. Notably, IDH1mut patients showed no significant OS difference (P = .153), whereas IDH2mut patients exhibited significantly shorter overall survival (OS) than IDHwt patients (HR = 1.844, 95 % CI: 1.008-3.792, P = .047). Additionally, IDH1mut patients with DNMT3A co-mutations also demonstrated shorter DFS and OS (P = .013 and P = .003, respectively), while IDH2mut patients with co-mutations in NPM1, ASXL1, or SRSF2 had reduced disease-free survival (DFS) and OS (P < .05). These findings suggest that early detection of IDH1/2 mutations and associated clinical features at AML diagnosis could provide a rationale for targeted therapy with IDH inhibitors, potentially improving patient outcomes.