Abstract
Several genetic risk classification systems based on response to older acute myeloid leukemia patients treated with less-intensive regimens, especially venetoclax (VEN) + hypomethylating agent (HMA), are proposed recently. VEN+HMA improved the outcome of cytogenetic adverse-risk AML, AML with some of MR mutations and/or clonal hematopoiesis (CH) related mutations. DNMT3A (mut), IDH1/2 (mut) and NPM1 (mut) were defined as "VEN sensitive mutations". DDX41 (mut) is identified as a particularly favorable-risk group. Even multi-hit TP53 status did not negatively affect overall survival (OS) of DDX41-mutants. Signaling gene mutations (FLT3-ITD(pos) and K/NRAS (mut)) are classified as intermediate risk, consistent with their biological associations as mediators of VEN resistance.