Jiang Moqin, Chen Meng, Liu Qian, Jin Zhiling, Yang Xiangdong, Zhang Weifeng
Department of Hematology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Front Oncol. 2023 Mar 17;13:1116438. doi: 10.3389/fonc.2023.1116438. eCollection 2023.
Myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by ineffective hematopoiesis and dysplasia of the myeloid cell lineage and are characterized by peripheral blood cytopenia and an increased risk of transformation to acute myeloid leukemia (AML). Approximately half of the patients with MDS have somatic mutations in the spliceosome gene. Splicing Factor 3B Subunit 1A (SF3B1), the most frequently occurring splicing factor mutation in MDS is significantly associated with the MDS-RS subtype. SF3B1 mutations are intimately involved in the MDS regulation of various pathophysiological processes, including impaired erythropoiesis, dysregulated iron metabolism homeostasis, hyperinflammatory features, and R-loop accumulation. In the fifth edition of the World Health Organization (WHO) classification criteria for MDS, MDS with SF3B1 mutations has been classified as an independent subtype, which plays a crucial role in identifying the disease phenotype, promoting tumor development, determining clinical features, and influencing tumor prognosis. Given that SF3B1 has demonstrated therapeutic vulnerability both in early MDS drivers and downstream events, therapy based on spliceosome-associated mutations is considered a novel strategy worth exploring in the future.
骨髓增生异常综合征（MDS）是克隆性血液系统恶性肿瘤，其特征为造血无效以及髓系细胞系发育异常，外周血细胞减少以及转化为急性髓系白血病（AML）的风险增加。大约一半的MDS患者在剪接体基因中有体细胞突变。剪接因子3B亚基1A（SF3B1）是MDS中最常见的剪接因子突变，与MDS-RS亚型显著相关。SF3B1突变密切参与MDS对各种病理生理过程的调控，包括红细胞生成受损、铁代谢稳态失调、高炎症特征和R环积累。在世界卫生组织（WHO）MDS分类标准的第五版中，具有SF3B1突变的MDS已被归类为一个独立的亚型，这在识别疾病表型、促进肿瘤发展、确定临床特征和影响肿瘤预后方面起着关键作用。鉴于SF3B1在早期MDS驱动因素和下游事件中均显示出治疗易损性，基于剪接体相关突变的治疗被认为是未来值得探索的一种新策略。
