Genetic study on refractory anemia group of myelodysplastic syndromes MDS RA

Abstract

Myelodysplastic syndromes (MDS) are clonal disorders characterized by ineffective hematopoiesis and peripheral cytopenias [1] and reported as hematological malignancy of all age groups including childhood. Generally, morphological examination of marrow smear remains the cornerstone of diagnosis of MDS. In ambiguous cases, a cytogenetic evaluation is suggested to correlate morphological findings and confirm diagnosis. While, the diagnosis of MDS is also complemented by cytogenetics [2], there are no cytogenetic abnormalities specific or consistent for any morphologic subgroup of MDS. Chromosomal abnormalities would ultimately lead to the discovery of the genetic lesions important in the pathogenesis of MDS. Existing therapeutic options for MDS patients include supportive care, low/highintensity therapy. However, therapeutic dilemmas exist because of disease heterogeneity and patient age. Hence, development of an effective therapeutic protocol inevitably requires additional investigations in understanding the initial genetic event of the presumed multi-step pathogenesis of MDS. Molecular studies suggest that pathogenetic lesions in MDS relate to ineffective hematopoiesis and enhanced apoptosis of hemopoietic cells within MDS marrow. Hence, signaling molecules and the pathways involved in mediating apoptosis was extensively analyzed and a hypothesis was developed that in addition to pro-inflammatory cytokines such as tumor necrosis factoralpha newline(TNF- and#61537;), tumor necrosis factor-beta (TNF- and#61538;) and interferon-gamma (INF- and#61543;), transcription factors like NF-and#954;B also involve/influence the pathogenesis of MDS [3]. It has been demonstrated that polymorphisms in genes of cytokines might have direct functional significance by altering level of genes expression and/or its function in many types of cancer [4].