DDX41是与遗传易感相关的骨髓肿瘤中最常见的突变基因，包括骨髓增生异常综合征（MDS）和急性髓系白血病（AML）。我们对3795名患有骨髓肿瘤的患者进行了分析，发现其中151名（4%）携带DDX41变异并被诊断为AML（n＝96）、MDS（n＝52）和慢性髓系单核细胞白血病（n＝3）。最常见的DDX41变异是体细胞变异p.R525H，其次是生殖系变异p.M1I和p.D140fs。大多数肿瘤具有正常核型（59%），最常见的共突变是TP53（16%）和ASXL1（15%）。除DDX41变异外，30%的患者没有伴发突变。患有骨髓恶性肿瘤和DDX41变异的患者对治疗反应良好，治疗原发AML和MDS的患者总体反应率分别为87%和84%。治疗纯化AML或MDS的患者的中位总生存期(mOS)分别为49个月和71个月。接受含维奈克替（venetoclax）等低强度方案治疗的AML患者具有较好的生存率（2年生存率：91% vs. 60%，p＝.02），较低的复发累积发生率（10% vs. 56%，p＝.03），相比之下未接受维奈克替治疗的患者。在接受造血干细胞移植的患者中，AML和MDS的2年生存率分别为80%和85%。© 2023 Wiley Periodicals LLC.

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides DDX41 mutation. Patients with myeloid malignancies and DDX41 variants responded well to therapy, with an overall response rate for patients with treatment naïve AML and MDS of 87% and 84%, respectively. The median overall survival (mOS) of patients with treatment-naïve AML or MDS was 49 and 71 months, respectively. Patients with AML treated with low-intensity regimens including venetoclax had an improved survival (2-year OS 91% vs. 60%, p = .02) and lower cumulative incidence of relapse compared to those treated without venetoclax (10% vs. 56%, p = .03). In the 33% of patients receiving hematopoietic stem cell transplantation, the 2-year OS was 80% and 85% for AML and MDS, respectively.© 2023 Wiley Periodicals LLC.