Zhang Fenghong, Liu Yizi, Zhu Yiyan, Wang Qingyuan, Zhao Xiangyu, Wang Qian, Chen Yu, Chen Suning
National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
Department of Hematology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, People's Republic of China.
Leuk Lymphoma. 2025 Apr;66(4):753-763. doi: 10.1080/10428194.2024.2441855. Epub 2025 Jan 2.
Alterations in the RAS pathway underscore the pathogenic complexity of acute myeloid leukemia (AML), yet the full spectrum, including , , , , and , remains to be fully elucidated. In this retrospective study of 735 adult AML patients, the incidence of RAS pathway alterations was 32.4%, each with distinct clinical characteristics. Venetoclax combined with hypomethylating agents (VEN + HMA) did not significantly improve response rates compared to intensive chemotherapy (IC) group. In the IC group, mutations in the N-SH2 domain showed a trend toward poorer prognosis, though not statistically significant in multivariate analysis, while mutations correlated with improved outcomes. In the VEN + HMA group, mutations in the N-SH2 domain emerged as an independent adverse prognostic marker. or mutations showed no survival advantage compared to wild-type, aligning with their intermediate-risk classification in the 2024 ELN guidelines. These findings emphasize the need for treatment-specific risk stratification for RAS pathway mutations in AML.
RAS 通路的改变突显了急性髓系白血病（AML）的致病复杂性，然而其全貌，包括[具体内容缺失]，仍有待充分阐明。在这项对 735 例成年 AML 患者的回顾性研究中，RAS 通路改变的发生率为 32.4%，每种改变都有独特的临床特征。与强化化疗（IC）组相比，维奈克拉联合低甲基化药物（VEN + HMA）并未显著提高缓解率。在 IC 组中，N-SH2 结构域的[具体突变缺失]突变显示出预后较差的趋势，尽管在多变量分析中无统计学意义，而[具体突变缺失]突变与较好的预后相关。在 VEN + HMA 组中，N-SH2 结构域的[具体突变缺失]突变成为独立的不良预后标志物。与野生型相比，[具体突变缺失]或[具体突变缺失]突变未显示出生存优势，这与它们在 2024 年欧洲白血病网络（ELN）指南中的中危分类一致。这些发现强调了对 AML 中 RAS 通路突变进行针对治疗的风险分层的必要性。
