Maher Michael, Diesch Jeannine, Le Pannérer Marguerite-Marie, Buschbeck Marcus
Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, 08916 Badalona, Spain.
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, 08916 Badalona, Spain.
Cancers (Basel). 2021 Apr 6;13(7):1746. doi: 10.3390/cancers13071746.
Mutations in genes encoding chromatin regulators are early events contributing to developing asymptomatic clonal hematopoiesis of indeterminate potential and its frequent progression to myeloid diseases with increasing severity. We focus on the subset of myeloid diseases encompassing myelodysplastic syndromes and their transformation to secondary acute myeloid leukemia. We introduce the major concepts of chromatin regulation that provide the basis of epigenetic regulation. In greater detail, we discuss those chromatin regulators that are frequently mutated in myelodysplastic syndromes. We discuss their role in the epigenetic regulation of normal hematopoiesis and the consequence of their mutation. Finally, we provide an update on the drugs interfering with chromatin regulation approved or in development for myelodysplastic syndromes and acute myeloid leukemia.
编码染色质调节因子的基因突变是早期事件，促成了具有不确定潜能的无症状克隆性造血及其向严重程度不断增加的髓系疾病的频繁进展。我们关注包括骨髓增生异常综合征及其向继发性急性髓系白血病转化在内的髓系疾病子集。我们介绍了染色质调节的主要概念，这些概念为表观遗传调控提供了基础。更详细地说，我们讨论了在骨髓增生异常综合征中频繁发生突变的那些染色质调节因子。我们讨论了它们在正常造血表观遗传调控中的作用以及它们突变的后果。最后，我们提供了关于已批准或正在研发的用于治疗骨髓增生异常综合征和急性髓系白血病的干扰染色质调节的药物的最新信息。
