Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia.

(1) Runt-related transcription factor 1 () mutations in acute myeloid leukemia (AML) are often associated with worse prognosis. We assessed co-occurring mutations, response to therapy, and clinical outcomes in patients with and without mutant (); (2) We analyzed 328 AML patients, including 177 patients younger than 65 years who received intensive chemotherapy and 151 patients >65 years who received hypomethylating agents. and co-existing mutations were identified using next-generation sequencing; (3) mutations were identified in 5.1% of younger patients and 15.9% of older patients, and were significantly associated with increasing age ( = 0.01) as well as intermediate-risk cytogenetics including normal karyotype ( = 0.02) in the elderly cohort, and with lower lactate dehydrogenase (LDH; = 0.02) and higher platelet count ( = 0.012) overall. Identified co-occurring mutations were primarily mutations in older patients and mutations in younger patients; FLT3-ITD and IDH1/2 co-mutations were also frequent. Younger AML patients treated with intensive chemotherapy experienced inferior treatment outcomes. In older patients with AML treated with hypomethylating agent (HMA) therapy, response and survival was independent of status. Older patients with prior myelodysplastic syndrome or myeloproliferative neoplasms (MDS/MPN) had particularly dismal outcome. Future studies should focus on the prognostic implications of mutations relative to other co-occurring mutations, and the potential role of hypomethylating agents for this molecularly-defined group.