组蛋白甲基化修饰在多发性骨髓瘤发生发展中的作用研究进展

Role of histone methylation in the development of multiple myeloma

多发性骨髓瘤(multiple myeloma,MM)是一类骨髓浆细胞恶性克隆性疾病。尽管MM的治疗有所进展,但大部分患者均会复发或耐药,因此亟需新的治疗靶点。除了遗传缺陷和骨髓微环境紊乱外,越来越多的证据表明表观遗传学调控异常在MM发病中发挥重要作用。表观遗传因子的突变往往与基因组不稳定、耐药性和疾病进展有关,且这些突变在治疗后有所增加,尤其是组蛋白甲基化和DNA甲基化修饰酶。本文就组蛋白甲基化修饰在MM中的作用进行综述,重点讨论组蛋白甲基化转移酶(histone methyltransferases,HMTs)和组蛋白去甲基化酶(histone demethylases,HDMs)在MM发生发展中的作用。

Multiple myeloma(MM) is a malignant clonal disease of the plasma cells in bone marrow. Despite the progress of MM treatment, almost all patients will relapse or become resistant to the prescribed drugs. As such, new treatment targets are urgently needed. As well as genetic defects and bone marrow microenvironment disorders, increasing evidence shows that epigenetic regulation plays an important role in MM. Studies have shown that mutations in epigenetic factors are often related to genomic instability,drug resistance and disease progression. These mutations have been found to increase after treatment, particularly histone methylation and DNA methylation modifying enzymes. Here, we reviewed the progress in histone methylation modification in MM, in particular the role of histone methyltransferases(HMTs) and histone demethylases(HDMs) in the development of MM.