Overexpression of Pro-Inflammatory Cytokines in Myelodysplastic Syndrome (MDS-RA)

Myelodysplastic syndromes (MDS) are clonal disorders characterized ineffective hematopoiesis and subsequent progression to acute myeloid leukemia (AML). Among the subtypes of MDS, refractory anemia (RA) and refractory anemia with ringed sideroblasts exhibits ineffective hematopoiesis consistently. However, an apparent paradox in early MDS is that these disorders presents with peripheral cytopenia, despite having normo or hypercellular bone marrow. This inconsistency could be explained by the premature programmed cell death of a large numbers of cells in the BM before they enter the peripheral system. 

This signifies an unfavorable bone marrow microenvironment for cell proliferation and maturation in early MDS, unlike in leukemia where the cell proliferation exceeds apoptosis and the marrow environment favors cell division.Although it is well established that MDS arises from an intrinsic or acquired genetic defect in hematopoietic stem cells leading to clonal expansion of a stem cell population; it has also been suggested that other epigenetic abnormalities such as aberrant cytokine production, altered stem cell adhesion, or an abnormal marrow microenvironment might contribute to the disease biology. Read more>>>>>>>>>>>>>>>>>>