Number of RUNX1 mutations, wild-type allele loss and additional mutations impact on prognosis in adult RUNX1-mutated AML

RUNX1 -mutated acute myeloid leukemia (AML) show a distinct pattern of genetic abnormalities and an adverse prognosis. We analyzed the impact of multiple RUNX1 mutations and RUNX1 wild-type (WT) loss in 467 AML with RUNX1 mutations (mut): (1) RUNX1 WT loss ( n =53), (2) >1 RUNX1 mut ( n =94) and (3) 1 RUNX1 mut ( n =323). In 1 RUNX1 mut, +8 was most frequent, whereas in WT loss +13 was the most abundant trisomy (+8: 66% vs 31%, P =0.022; +13: 15% vs 62%, P 1 RUNX1 mut (14 months) showed an adverse impact on prognosis compared with 1 RUNX1 mut (22 months; P =0.002 and 0.048, respectively). Mutations in ASXL1 and ⩾2 additional mutations correlated with shorter OS (10 vs 18 months, P =0.028; 12 vs 20 months, P =0.017). Thus, the number of RUNX1 mut, RUNX1 WT loss and the number and type of additional mutations is biologically and clinically relevant.