OVEREXPRESSION OF TUMOR-NECROSIS-FACTOR (TNF)-ALPHA AND INTERFERON (IFN)-GAMMA BY BONE-MARROW CELLS FROM PATIENTS WITH MYELODYSPLASTIC SYNDROMES

To clarify whether regulatory cytokines inhibit hematopoiesis in patie nts with myelodysplastic syndromes (MDS), malignancies characterized b y the formation of cytopenias despite the presence of cellular bone ma rrow, expression of TNF-alpha and IFN-gamma by bone marrow cells was i nvestigated using specific reverse transcriptase-polymerase chain reac tion assays. An enhanced expression of the mRNA for TNF-alpha was obse rved in most of the samples from MDS patients (11/14, 79%), whereas no enhancement was observed in bone marrow samples from AML (0/6), CML ( 0/2) or control cases (0/8). The expression of IFN-gamma was also enha nced in some of MDS cases (5/12, 42%) while AML (0/5), CML (0/2) and c ontrol cases (0/6) showed very low levels of IFN-gamma mRNA expression . Immunohistochemical examination confirmed the scattered presence of TNF-alpha or IFN-gamma producing cells in the bone marrow of MDS patie nts. The majority of these cells were CD68-positive macrophage lineage cells. These results suggested that disruption of hematopoiesis in MD S might be caused by enhanced production of inhibitory regulatory cyto kines especially TNF-alpha and occasionally IFN-gamma by bone marrow m acrophages.