表观遗传学畸变与miRNAs相互作用在骨髓瘤中的研究进展

Role of epigenetics/miRNAs interaction in multiple myeloma

多发性骨髓瘤(multiple myeloma,MM)是以骨髓中克隆性浆细胞异常增生并分泌大量单克隆免疫球蛋白或其片段(M蛋白)为特征的后生发中心B细胞恶性肿瘤。MM细胞在骨髓中定植、克隆性增殖,进而分泌单克隆蛋白,导致贫血、溶骨性损害、肾功能不全及免疫功能受抑等临床症状。随着硼替佐米等蛋白酶体抑制剂,沙利度胺、雷利度胺等免疫调节剂,激素及烷化剂等新药相继应用于临床,MM患者的总体生存期得到明显延长,但复发及耐药性形成仍是妨碍MM得以根治的巨大难.

With the development of novel agents,multiple myeloma(MM)still remains incurable due to relapse or refractory drug resistance.Thus,it is crucial to further investigate the complex mechanisms of MM pathogenesis,and provide more effective therapeutic strategies.Not only genetic aberrations,but also epigenetic modifications have been shown to be involved in the disrupted cancer pathways,and MM highly heterogeneity.Notably,epigenetic silencing of miRNAs is well documented via DNA methylation,histone modification,etc.Conversely,several miRNAs,recently described as'epi-miRNAs',directly target epigenetic markers.Therefore,combination of miRNAs mimics with inhibitors of epigenetic modifiers would be a more potent therapeutic strategy in relapse or refractory MM patients.In this review,we will discuss the advances of research on epigenetics/miRNAs interaction in MM.