Iwama Atsushi
Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University.
Rinsho Ketsueki. 2017;58(6):654-660. doi: 10.11406/rinketsu.58.654.
Epigenetic regulation holds a key role in gene expression due to its modulation of the structure and function of chromatin. Notably, epigenetic dysregulation is deeply involved in the pathogenesis of hematological malignancies. Polycomb group (PcG) genes encoding histone modifier proteins are representative epigenetic genes that regulate a variety of cellular functions, including self-renewal and multi-lineage differentiation of stem cells. Surprisingly, many PcG genes are targeted by deletions or somatic mutations or both in a number of hematological malignancies, such as myelodysplastic syndrome (MDS). PcG proteins form multiprotein complexes and exert either oncogenic or tumor-suppressive functions, depending on the tumor type. In MDS, they function as tumor suppressors. This review summarizes the current knowledge on deregulated polycomb function in the pathogenesis of MDS.
表观遗传调控因其对染色质结构和功能的调节而在基因表达中起着关键作用。值得注意的是，表观遗传失调与血液系统恶性肿瘤的发病机制密切相关。编码组蛋白修饰蛋白的多梳蛋白家族（PcG）基因是典型的表观遗传基因，可调节多种细胞功能，包括干细胞的自我更新和多谱系分化。令人惊讶的是，在许多血液系统恶性肿瘤中，如骨髓增生异常综合征（MDS），许多PcG基因会被缺失或体细胞突变或两者同时靶向。PcG蛋白形成多蛋白复合物，并根据肿瘤类型发挥致癌或肿瘤抑制功能。在MDS中，它们发挥肿瘤抑制作用。本综述总结了目前关于MDS发病机制中多梳蛋白功能失调的知识。
