亚砷酸对多发性骨髓瘤及p38通路的作用

The effects of arsenic trioxide on multiple myeloma and p38 MAPK pathway

多发性骨髓瘤(MM)是B细胞分化终末阶段的恶性血液病。尽管新药的研发和应用明显地提高了MM的治疗效果,但是复发、耐药等的频繁发生使得MM仍不可治愈。目前应用亚砷酸治疗MM受到广泛关注。亚砷酸可通过多种分子机制产生抗MM的效应,且其单药及联合方案均得到一定效果。但是,治疗过程中耐药性的产生较大地削减了亚砷酸的治疗效应,而近来研究显示p38通路的活化在亚砷酸引发的骨髓瘤细胞耐药性中发挥至关重要的作用。因此,本文就亚砷酸抗MM机制及p38通路在其中的作用进行综述,以期提高亚砷酸治疗MM的效果,为MM的治疗提供新的思路。

Multiple myeloma(MM)is a clonal B-cell malignancy with an age-adjusted incidence,ranking the second most frequent hematological malignancy in many countries.Even though the advent of novel agents including bortezomib have nearly doubled the median survival time in the past decade,MM largely remains incurable with an eventual relapse of the disease and resistance to therapy.To date,arsenic trioxide(ATO)has been applied to treat MM and its multiple molecular mechanisms can effectively target complex pathogenesis and pathways of MM.However,low response rate and relatively common resistance to ATO remain challenging issues indicated by trials.Recently,p38 mitogen-activated protein kinase(MAPK)activation by ATO was suggested to contribute to the resistance of MM cells to ATO treatment and inhibition of p38 MAPK pathway could significantly enhance ATO-induced cytotoxicity in MM cells.Therefore,targeting p38 MAPK pathway could be the new way to increase the treatment efficacy of ATO and improve the treatment outcome in MM.