DataSheet_1_CD7-positive leukemic blasts with DNMT3A mutations predict poor prognosis in patients with acute myeloid leukemia.docx

BackgroundDNMT3A mutations can be detected in premalignant hematopoietic stem cells and are primarily associated with clonal hematopoiesis of indeterminate potential; however, current evidence does not support assigning them to a distinct European Leukemia Net (ELN) prognostic risk stratification. CD7 is a lymphoid antigen expressed on blasts in approximately 30% of acute myeloid leukemia (AML), and its role in AML remains unclear and depends on subgroup evaluation. This study investigated the prognostic value of DNMT3A mutation combined with CD7 expression in AML.
MethodsWe retrospectively analyzed the clinical data of 297 newly diagnosed non-M3 AML patients. According to the DNMT3A mutation and CD7 expression in AML cells, patients were divided into the DNMT3A-mutated/CD7-positive (CD7+), DNMT3A-mutated/CD7-negative (CD7-), DNMT3A-wild-type/CD7+, and DNMT3A-wild-type/CD7- groups.
ResultsThe DNMT3A-mutated/CD7+ group had lower complete remission rates and higher relapse rates. Importantly, these patients had significantly shorter overall survival (OS) and relapse-free survival (RFS). Furthermore, multivariate analysis showed that CD7+ with DNMT3A mutation was an independent risk factor for OS and RFS.
ConclusionCD7+ with DNMT3A mutation predicts a poor prognosis in AML patients, and the immunophenotype combined with molecular genetic markers can help to further refine the current risk stratification of AML.

背景 DNMT3A突变（DNMT3A mutation）可在癌前造血干细胞中检出，其主要与意义未明的克隆性造血相关；但目前的证据不支持将其归为独立的欧洲白血病网（European Leukemia Net, ELN）预后风险分层体系。CD7是一种表达于原始细胞的淋巴系抗原，约30%的急性髓系白血病（acute myeloid leukemia, AML）患者的原始细胞可表达该抗原，其在AML中的作用仍不明确，且需结合亚组分析进行评估。本研究探讨了DNMT3A突变联合CD7表达在AML中的预后价值。
方法 本研究回顾性分析了297例初诊非M3型AML患者的临床资料。根据AML细胞的DNMT3A突变状态与CD7表达情况，将患者分为DNMT3A突变/CD7阳性（CD7+）组、DNMT3A突变/CD7阴性（CD7-）组、DNMT3A野生型/CD7阳性（CD7+）组以及DNMT3A野生型/CD7阴性（CD7-）组。
结果 DNMT3A突变/CD7阳性组的完全缓解率更低，复发率更高。值得注意的是，该组患者的总生存期（overall survival, OS）与无复发生存期（relapse-free survival, RFS）均显著缩短。进一步的多因素分析显示，CD7阳性联合DNMT3A突变是OS与RFS的独立危险因素。
结论 CD7阳性联合DNMT3A突变可提示AML患者存在不良预后，免疫表型联合分子遗传学标志物有助于进一步优化当前AML的预后风险分层体系。