Measurement of mRNA expression for a variety of cytokines and its receptors in bone marrows of patients with myelodysplastic syndromes

Background: Myelodysplastic syndromes (MDS) ale a group of disorders charac terized by ineffective and dysplastic haemopoiesis. Previous studies in the lab have shown extensive apoptosis and high levels of transforming growth factor (TGF-beta) and tumor necrosis factor (TNF-alpha) in the stromal laye r of MDS bone marrow. The current study focuses on the cytokines expressed in the bone marrow parenchymal cells. Materials and Methods: Bone marrow as pirate from 5 normal donors and 26 patients with myelodysplastic syndromes were examined for mRNA expression of tumor necrosis factor alpha (TNF-alpha ), macrophage colony stimulating factor (M-CSF), Flt-3 Ligand (Flt-3L), Flt -3 receptor (Flt-3 rec), interleukin 1 beta (IL 1 beta) and interleukin 1 r eceptor antagonist (IL-1 ra). Results: Comparison of 26 MDS marrows with 5 normals showed a significantly higher value for Flt-3 rec and IL 1 beta (p = 0.031 and p = 0.031) in the former while only Flt-1 beta rec was consider ably higher (p = 0.016) in newly diagnosed patients. In previously diagnose d group, Flt-3 rec (p = 0.001), TNF-alpha (p = 0.04) and IL-1 beta (p = 0.0 16) were higher than normal while there was no statistically significant di fference in the newly versus previously diagnosed MDS cases: Conclusion: mR NA expression of all six cytokines measured were considerably higher in MDS when compared to normal and that these levels tend to increase with diseas e duration. The precise source of these cytokines as well as their role in MDS pathogenesis remains to be determined, but this study confirms our prev ious reports that there is no dearth of cytokines in these bizarre myelosup pressive states.