In a second external cohort of 117 ND‐AML patients (median age 74 years, 60% males) treated with Ven‐HMA at the University of Chicago (UOC), 45 of 113 (40%) of informative cases harbored adverse karyotype; 2 (2%) with KMT2Ar; mutations involved TP53 (30%), RUNX1 (22%), IDH1/2 (11%), NPM1 (10%), FLT3‐ITD (9%), DDX41 (3%). Here, DDX41 is linked to acute myeloid leukemia.