Bhattacharyya Teerna, Bond Jonathan
Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, D04V1W8 Dublin 4, Ireland.
Children's Health Ireland at Crumlin, Crumlin, D12N512 Dublin 12, Ireland.
Cancers (Basel). 2023 Mar 9;15(6):1693. doi: 10.3390/cancers15061693.
Epigenetic dysregulation is a hallmark of many haematological malignancies and is very frequent in acute myeloid leukaemia (AML). A cardinal example is the altered activity of the Polycomb Repressive Complex 2 (PRC2) due to somatic mutations and deletions in genes encoding PRC2 core factors that are necessary for correct complex assembly. These genetic alterations typically lead to reduced histone methyltransferase activity that, in turn, has been strongly linked to poor prognosis and chemoresistance. In this review, we provide an overview of genetic alterations of PRC components in AML, with particular reference to structural and functional features of PRC2 factors. We further review genetic interactions between these alterations and other AML-associated mutations in both adult and paediatric leukaemias. Finally, we discuss reported prognostic links between PRC2 mutations and deletions and disease outcomes and potential implications for therapy.
表观遗传失调是许多血液系统恶性肿瘤的一个标志，在急性髓系白血病（AML）中非常常见。一个典型的例子是多梳抑制复合体2（PRC2）的活性改变，这是由于编码PRC2核心因子的基因发生体细胞突变和缺失，而这些核心因子是正确组装复合体所必需的。这些基因改变通常会导致组蛋白甲基转移酶活性降低，进而与预后不良和化疗耐药性密切相关。在这篇综述中，我们概述了AML中PRC组分的基因改变，特别提及PRC2因子的结构和功能特征。我们还进一步综述了这些改变与成人和儿童白血病中其他AML相关突变之间的基因相互作用。最后，我们讨论了报道的PRC2突变和缺失与疾病预后的关联以及对治疗的潜在影响。
