Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epigenetics refers to the study of clonally inherited changes in gene expression without accompanying genetic changes. Previous research on the epigenetics of myelodysplastic syndromes (MDS) mainly focused on the inactivation of tumor suppressor genes as a result of DNA methylation. However, the basic molecular pathogenesis of epigenetics in MDS remains poorly understood. Recent studies have revealed that DNA methylation and histone modification may be controlled by Polycomb-group (PcG) proteins, which may give new clues toward understanding the epigenetic mechanism of MDS. In this study, we explored for the first time the expression of PcG genes, including EZH2, EED, SUZ12, RING1, and BMI1, in various MDS subsets and acute myeloid leukemia (AML), as well as the relationship between the expression of PcG genes and epigenetic alteration and prognosis-risk scoring. Patients with MDS/AML showed overexpression of EZH2, RING1, and BMI1 genes compared to their expression levels in patients with non-clonal cytopenia diseases. The MDS patients with DNA methylation had higher EZH2 expression than those without DNA methylation. The patients who received decitabine treatment presented significantly reduced expression of EZH2 and RING1 besides decreased p15(INK4B) methylation after decitabine treatment. Moreover, overexpression of EZH2, RING1, and BMI1 was always linked to poor prognostic scoring. In conclusion, overexpression of the EZH2, RING1, and BMI1 genes is common in MDS and indicate poor prognosis. The products of these genes might participate in epigenetic regulation of MDS. These studies may also contribute to our understanding of the effective mechanism of decitabine.
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PMID:Overexpression of the EZH2, RING1 and BMI1 genes is common in myelodysplastic syndromes: relation to adverse epigenetic alteration and poor prognostic scoring. 2112 1

Genetic lesions affecting epigenetic regulators are frequent in myelodysplastic syndromes (MDS). Polycomb proteins are key epigenetic regulators of differentiation and stemness that act as two multimeric complexes termed polycomb repressive complexes 1 and 2, PRC1 and PRC2, respectively. While components and regulators of PRC2 such as ASXL1 and EZH2 are frequently mutated in MDS and AML, little is known about the role of PRC1. To analyze the role of PRC1, we have taken a functional approach testing PRC1 components in loss- and gain-of-function experiments that we found overexpressed in advanced MDS patients or dynamically expressed during normal hematopoiesis. This approach allowed us to identify the enzymatically active component RING1A as the key PRC1 component in hematopoietic stem cells and MDS. Specifically, we found that RING1A is expressed in CD34+ bone marrow progenitor cells and further overexpressed in high-risk MDS patients. Knockdown of RING1A in an MDS-derived AML cell line facilitated spontaneous and retinoic acid-induced differentiation. Similarly, inactivation of RING1A in primary CD34+ cells augmented erythroid differentiation. Treatment with a small compound RING1 inhibitor reduced the colony forming capacity of CD34+ cells from MDS patients and healthy controls. In MDS patients higher RING1A expression associated with an increased number of dysplastic lineages and blasts. Our data suggests that RING1A is deregulated in MDS and plays a role in the erythroid development defect.
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PMID:Polycomb protein RING1A limits hematopoietic differentiation in myelodysplastic syndromes. 2938 37