Prognosis and risk factors for <scp><i>ASXL1</i></scp> mutations in patients with newly diagnosed acute myeloid leukemia and myelodysplastic syndrome
Liqing Yang, Xiaoyu Wei, Yuping Gong
Abstract
Abstract Objective The objective of the study was to determine the prognosis and risk factors for additional sex combs like 1 ( ASXL1 ) mutations in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Population and Methods This retrospective study enrolled 219 adult patients with newly diagnosed AML and MDS, who were treated in West China Hospital from October 2018 to January 2022. The primary clinical outcome was evaluated by overall survival (OS) followed up to January 2023. Kaplan–Meier analysis and Cox multivariate regression analysis were performed to identify potential prognostic parameters in patients with ASXL1 mutations (mt). Results A total of 34 (15.53%) ASXL1 mt were detected, which occurred more frequently in the elderly and MDS cohorts ( p < 0.001). Significantly lower blasts% ( p < 0.001) and higher frequencies of mutant RUNX1 , SRSF2 , STAG2 , EZH2 , and SETBP1 ( p < 0.02) were observed in the ASXL1 mt cohort. Patients with ASXL1 mt manifested with a worse complete remission rate ( p = 0.011), and an inferior OS was shown in subgroups with MDS, co‐mutations of RUNX1 , SRSF2 , or NRAS , as well as mutations in G646W ( p < 0.05). Multivariate analysis considering age, diagnosis, co‐mutations, and mutation site confirmed an independently adverse prognosis of mutations in G646W (HR = 4.302, 95% CI: 1.150–16.097) or RUNX1 co‐mutations (HR = 4.620, 95% CI: 1.385–15.414) in the ASXL1 mt cohort. Conclusion Our study indicated that mutations in G646W or RUNX1 co‐mutations are closely associated with a dismal clinical outcome in patients with AML and MDS harboring ASXL1 mt . Considering the poor prognosis and risk factors in patients with ASXL1 mt , more available treatments should be pursued.