Fujino Takeshi
Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo.
Rinsho Ketsueki. 2022;63(6):561-572. doi: 10.11406/rinketsu.63.561.
Somatic mutations in the epigenetic regulator ASXL1 are considered a poor prognostic factor in myeloid malignancies, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). ASXL1 mutations coexist with other mutations in majority of patients, suggesting that its mutation alone is insufficient to cause cancer. ASXL1 mutations have been detected in age-related clonal hematopoiesis (CH), which has been linked to an increased risk of hematological malignancies. Therefore, ASXL1 mutations are likely to be one of the first events in the tumorigenesis process. With our most recent findings, we summarize the mechanisms by which ASXL1 mutations cause CH and hematological malignancies in this review.
表观遗传调节因子ASXL1中的体细胞突变被认为是髓系恶性肿瘤(包括骨髓增生异常综合征(MDS)和急性髓系白血病(AML))的不良预后因素。在大多数患者中,ASXL1突变与其他突变共存,这表明仅其突变不足以引发癌症。在与年龄相关的克隆性造血(CH)中已检测到ASXL1突变,而CH与血液系统恶性肿瘤风险增加有关。因此,ASXL1突变很可能是肿瘤发生过程中的首批事件之一。在本综述中,我们结合最新研究结果总结了ASXL1突变导致CH和血液系统恶性肿瘤的机制。