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

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of disorders characterized 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 layer of MDS bone marrow. The current study focuses on the cytokines expressed in the bone marrow parenchymal cells. MATERIALS AND METHODS: Bone marrow aspirate 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 receptor 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 considerably higher (p = 0.016) in newly diagnosed patients. In previously diagnosed group, Flt-3 rec (p = 0.001), TNF-alpha (p = 0.04) and IL-1 beta (p = 0.016) were higher than normal while there was no statistically significant difference in the newly versus previously diagnosed MDS cases: CONCLUSION: mRNA expression of all six cytokines measured were considerably higher in MDS when compared to normal and that these levels tend to increase with disease duration. The precise source of these cytokines as well as their role in MDS pathogenesis remains to be determined, but this study confirms our previous reports that there is no dearth of cytokines in these bizarre myelosuppressive states.