Executive Summary : | Myelodysplastic syndromes (MDSs) are a pre-malignant, heterogeneous group of hematologic disorders usually with a poor clinical outcome and median overall survival of fewer than 2 years in higher risk subtypes of this disease. MDS are clonal stem cell disorders characterized by marrow hypercellularity, peripheral blood cytopenias, chronic anemia, dysplastic marrow changes, and ineffective hematopoiesis, with a high incidence of progression to Acute Myeloid Leukemia(AML). It's one of the classical bone marrow failure disorders. Increased apoptosis of hematopoietic progenitors is a hallmark of MDS. Erythroid apoptosis is thought to be one of the primary mechanisms underlying the severe anemia observed in the refractory anemia (RA) and RA with ringed sideroblasts (RARS). It is believed that the pathogenesis in MDS is associated with epigenetic alteration of blood stem cells resulting in changes in global gene expression. The methylome of a cell is determined by a fine balance of DNA methylation and demethylation. Mutations of genes involved in this process and the cross-talk between these genes in bringing out the adequate levels of DNA methylation are crucial in a cell's functioning. This becomes vital when the cell involved is a multipotent cell-like Hematopoietic Stem Cell, aberrant differentiation, leading to an abnormality in cells of multiple lineages. TET2 and DNMTs are among the commonly mutated genes in MDS (45% of MDS patients.DNA demethylating agents (e.g. 5-Azacytidine) are used in the treatment of MDS and AML. Amongst the ncRNA family, lncRNA and miRNA are the most thoroughly studied. LncRNAs represent another class of non-coding regulatory RNAs. LncRNAs are protein non-coding, usually 200 nt in length, and are located in the nucleus through cytoplasmic localization is also detected. LncRNAs are divided into five subtypes: Sense, Antisense, Bidirectional, Intronic, and Intergenic lncRNA These ncRNAs are believed to play a crucial role in hematopoiesis, lineage commitment, and epigenetic regulation. |