Ismail Nor Hayati, Mussa Ali, Zakaria Nur Atikah, Al-Khreisat Mutaz Jamal, Zahidin Muhamad Aidil, Ramli Noor Nabila, Mohammad Siti Nur Nabeela A'ifah, Hassan Rosline, Mohd Noor Noor Haslina, Iberahim Salfarina, Zulkafli Zefarina, Mohamed Yusoff Shafini, Husin Azlan, Johan Muhammad Farid
Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia.
Department of Biology, Faculty of Education, Omdurman Islamic University, Omdurman P.O. Box 382, Sudan.
Biomedicines. 2022 Oct 31;10(11):2767. doi: 10.3390/biomedicines10112767.
Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.
多发性骨髓瘤(MM)是一种极其复杂且异质性的疾病,由骨髓中起始的恶性单克隆浆细胞异常增殖所致。在疾病进展过程中,涉及一个包括分化、增殖和侵袭的多步骤过程。尽管近年来由于大量新型治疗药物的发现,治疗结果有了很大改善,但MM仍被视为一种无法治愈的疾病。MM患者面临缓解期伴有复发或进展的情况,最终不可避免地发展到难治阶段。在这方面,MM可能需要新的药物或治疗策略的调整以克服耐药性。多种基因异常(如点突变、易位和缺失)和表观遗传变化(如DNA甲基化、组蛋白修饰和非编码RNA)促成了MM的发病机制和发展。在此,我们综述表观遗传机制在MM发生发展中的重要作用。我们还强调表观遗传途径作为MM潜在的新型治疗途径,包括它们的相互作用、表观遗传抑制剂的使用以及在免疫肿瘤学中的主要参与情况。