Classification of Haematolymphoid Tumours (WHO-HAEM5), they are included in the criteria defining AML, myelodysplasia-related (AML-MR). 3 In addition, in the newly published International Consensus of Classification of myeloid neoplasms and acute leukemia (ICC), STM, together with RUNX1 mutation, define the entity of AML with myelodysplasia-related gene mutations. 4 However, the prognosis of STM in NPM1+ AML remains unclear. Wright et al. recently showed that STM positive (STM+) and STM negative (STMÀ) AML patients with mutated NPM1 who received intensive chemotherapy had no significant differences in overall survival (OS) and EFS, suggesting that STM+ NPM1+ AML should be categorized as AML with mutated NPM1. 5 Despite this recent study, the data on the prognostic impact of STM in NPM1+ AML remains limited. Thus, we sought to investigate the prognostic implications of STM, age, and treatment inWe conducted a comprehensive analysis with a single center cohort of 129 cases of NPM1+ AML diagnosed at our institution from March 2018 to November 2021. Therapy-related myeloid neoplasms, AML with MR cytogenetic abnormalities, 4 and AML with recurrent genetic abnormalities other than NPM1 mutations were excluded from the analysis. Cytogenetic testing, molecular genetic testing, and variant calling in NGS were performed according to previously described procedures. 6 The baseline characteristics of the study cohort were summarized in Table S1. Of the 129 patients with NPM1+ AML, 25 (19%) had STM (13 males and 12 females) (Figure 1A). Similar to findings by Wright et al., SRSF2 was the most common STM in our cohort (n = 13; 52%), followed by STAG2 (n = 6; 24%), U2AF1 (n = 4; 16%), SF3B1 (n = 3; 12%), BCOR and ASXL1(n = 1 each; 4%). EZH2 and ZRSR2 were not detected. RUNX1 was detected in four patients (3 [3%] without STM and 1 [4%] with STM).Other common (>10%) co-mutated genes in patients with STM were FLT3-ITD (32%), IDH2 (24%), FLT3-TKD (20%), DNMT3A (20%), TET2 (16%), IDH1 (16%), NRAS (16%), and PTPN11 (12%) (Figure 1B).Patients with STM were significantly older (median age at diagnosis of 71 years [range 47-89] vs. 61 years [range 28-87], p < .001) and had lower white blood cell count at diagnosis (median 6.1 Â 10 9 /L [0.9-164] vs 26.3 Â 10 9 /L [0.7-251], p = .002) compared to patients without STM. No significant differences between the two groups were found in hemoglobin levels, platelet levels, and bone marrow blast percentages at diagnosis (Table S1). Of the patients with STM, 15 (60%) received intensive chemotherapy, 6 (24%) received nonintensive treatment (5 with venetoclax and azacitidine and 1 with low-dose cytarabine), and 4 (16%) were offered the best supportive care. Complete remission (CR) was achieved in 14 patients (12 [80%] in intensively treated patients and 2 [33%] in non-intensively treated patients). Out of the 14 patients who achieved CR, 5 (36%) experienced relapse of the disease. Among the relapsed patients, one exhibited persistent NPM1, one lost NPM1, and NPM1 testing was not available for fo...