多发性骨髓瘤的表观遗传调控突变与表观遗传治疗
Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma.
作者信息
Dupéré-Richer Daphné, Licht Jonathan D
机构信息
Department of Medicine, Division of Hematology-Oncology and The University of Florida Health Cancer Center University of Florida, Gainesville, Florida, USA.
出版信息
Curr Opin Hematol. 2017 Jul;24(4):336-344. doi: 10.1097/MOH.0000000000000358.
PURPOSE OF REVIEW
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.
RECENT FINDINGS
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.
SUMMARY
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 immunomodulatory drugs and proteasome inhibitors may enhance efficacy of combination regimens in MM.
综述目的
对患者样本进行的下一代测序和大规模分析，使人们对多发性骨髓瘤（MM）有了更全面的认识，揭示表观遗传失调是MM发病机制中的一个突出因素。
最新发现
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甲基化谱与疾病阶段相关，并且在疾病复发时，某些类型的表观遗传修饰基因突变更为普遍，提示其在疾病进展中发挥作用。已经开发出许多靶向表观遗传机制调节因子的小分子药物，其中一些正在MM中进行临床试验。
总结
最近的研究结果表明，表观遗传靶向药物可能是治愈MM的重要策略。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。
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