Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma.

Next generation sequencing and large scale analysis of patient specimens has created a more complete picture of Multiple Myeloma (MM) revealing that epigenetic deregulation is a prominent factor in MM pathogenesis. Over half of MM patients have mutations in genes encoding epigenetic modifier enzymes. The DNA methylation profile of MM is related to the stage of the disease and certain classes of mutations in epigenetic modifiers are more prevalent upon disease relapse, suggesting a role in disease progression. Many small molecules targeting regulators of epigenetic machinery have been developed and clinical trials are underway for some of these in MM. Recent findings suggest that epigenetic targeting drugs could be an important strategy to cure MM. Combining these agents along with other strategies to affect the MM cell such as IMIDs and proteasome inhibitors may enhance efficacy of combination regimens in MM.

下一代测序以及对患者样本的大规模分析使多发性骨髓瘤（MM）的情况更为完整地呈现出来，揭示出表观遗传失调是MM发病机制中的一个重要因素。 超过半数的MM患者在编码表观遗传修饰酶的基因中存在突变。MM的DNA甲基化图谱与疾病阶段有关，并且某些类型的表观遗传修饰因子突变在疾病复发时更为常见，这表明其在疾病进展中起作用。许多针对表观遗传机制调节因子的小分子已被研发出来，其中一些在MM中的临床试验正在进行。 近期的研究结果表明，表观遗传靶向药物可能是治愈MM的一种重要策略。将这些药物与其他影响MM细胞的策略（如免疫调节药物和蛋白酶体抑制剂）联合使用，可能会提高MM联合治疗方案的疗效。