克隆造血相关基因突变影响 AML 患者造血干细胞移植后的急性移植物抗宿主病。
Clonal Hematopoiesis-Associated Gene Mutations Affect Acute Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation in AML Patients.
发表日期:2024 Jul 02
作者:
Xiaoxuan Wei, Sai Huang, Zhenyang Gu, Jing Liu, Meng Li, Xiangshu Jin, Jian Bo, Fei Li, Yu Jing, Xiaoning Gao, Liping Dou, Daihong Liu, Chunji Gao
来源:
Stem Cell Research & Therapy
摘要:
背景自从下一代测序(NGS)技术广泛应用以来,克隆造血(CH)相关基因突变与同种异体造血干细胞移植(allo-HSCT)之间的关系已得到广泛研究。然而,研究主要集中于供体CH突变与移植预后的关系,而缺乏对受体CH突变与急性移植物抗宿主病(aGVHD)关系的研究。材料和方法 我们分析了 196 名接受异基因 HSCT 的 AML 患者的 NGS 结果及其与 aGVHD 和预后的相关性。结果 共有 93 名(47.4%)患者存在 CH 突变。最常见的突变基因是 DNMT3A(196 个基因中的 28 个;14.3%)、TET2(196 个基因中的 22 个;11.2%)、IDH1(196 个基因中的 15 个;7.7%)、IDH2(196 个基因中的 14 个;7.1%)和 ASXL1(13 个基因) 196;6.6%)。年龄超过 45 岁且有 DTA 突变(DNMT3A、TET2 或 ASXL1)的患者 aGVHD 发生率较高。 DNMT3A 突变(但不伴有 TET2 或 ASXL1 突变)是 45 岁以上接受异基因 HSCT 患者发生 aGVHD 的独立危险因素。中位随访时间为 42.7 个月,CH 突变与总生存期和无白血病生存期无关。结论 DNMT3A 突变(而非 TET2 或 ASXL1 突变)与较高的 aGVHD 发生率相关。
BACKGROUND The relationship between clonal hematopoiesis (CH)-associated gene mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been extensively studied since next-generation sequencing (NGS) technology became widely available. However, research has mainly focused on the relationship between donor CH mutations and transplant prognosis, and research into the relationship between CH mutations in the recipient and acute graft-versus-host disease (aGVHD) is lacking. MATERIAL AND METHODS We analyzed NGS results and their correlation with aGVHD and prognosis in 196 AML patients undergoing allo-HSCT. RESULTS A total of 93 (47.4%) patients had CH mutations. The most frequently mutated genes were DNMT3A (28 of 196; 14.3%), TET2 (22 of 196; 11.2%), IDH1 (15 of 196; 7.7%), IDH2 (14 of 196; 7.1%), and ASXL1 (13 of 196; 6.6%). The incidence of aGVHD was higher in patients older than 45 years old with DTA mutations (DNMT3A, TET2 or ASXL1). DNMT3A mutation but not with TET2 or ASXL1 mutation was an independent risk factor for aGVHD in patients receiving allo-HSCT older than 45 years old. With a median follow-up of 42.7 months, CH mutations were not associated with overall survival and leukemia-free survival. CONCLUSIONS DNMT3A mutation, but not TET2 or ASXL1 mutation, was associated with higher incidence of aGVHD.