[Myelodysplastic neoplasms with acute myeloid leukemia-like mutations: clinical features, molecular profiles, and prognosis].

Objective: To investigate the clinical, laboratory, and prognostic features of myelodysplastic neoplasm (MDS) patients harboring acute myeloid leukemia (AML) -like mutations. Methods: We retrospectively analyzed clinical, molecular, and outcome data from 1 464 adults with primary MDS diagnosed at the Institute of Hematology and Blood Diseases Hospital from August 2016 to June 2024. Results: AML-like mutations were detected in 64 patients (4.4% ). Compared with patients without AML-like mutations, those with AML-like mutations were younger [median 50 (IQR 39-60) vs 56 (45, 65) years; P=0.001], more often female (51.6% vs 35.4% ; P=0.009), had higher bone marrow blast percentage [6.5% (3.0%, 10.5% ) vs 2.5% (1.0%, 7.0% ) ; P<0.001], a higher rate of normal karyotype (75.0% vs 48.1% ; P<0.001), and lower hemoglobin levels [73 (67, 82) g/L vs 80 (66, 98) g/L; P=0.006]. The AML-like group had a higher number of gene mutations than the non-AML-like group [3 (IQR 2-4) vs 2 (1, 3) ; P<0.001). It was enriched for mutations in NPM1, DNMT3A, WT1, PTPN11, NRAS, BCOR, FLT3, CEBPA, and MYC (all P<0.05) and had lower rates of U2AF1, ASXL1, and TP53 mutations (all P<0.05). Overall survival (OS) did not differ between groups (P=0.730) ; however, the AML-like group had significantly shorter leukemia-free survival (LFS) [19 months (95% CI: 13-25) vs 46 months (95% CI: 38-54) ; P=0.012] and a higher 2-year cumulative incidence of AML transformation [ (41.7±9.1) % vs (10.4±1.1) % ; P<0.001]. Within the AML-like group, OS, LFS, and cumulative incidence of AML transformation did not differ between patients with low blasts and those with excess blasts (IB). Multivariable Cox regression identified age ≥60 years and PTPN11 mutations as independent adverse prognostic factors for OS, while DNMT3A, PTPN11, and FLT3 mutations independently predicted leukemic transformation. Conclusions: MDS patients harboring AML-like mutations exhibit distinct clinical and molecular features and a higher risk of progression to AML.