Deregulated polycomb complex function in the pathogenesis of MDS.

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.