TUMOR-NECROSIS-FACTOR-ALPHA SUPPRESSES HEMATOPOIESIS IN CHILDREN WITHMYELODYSPLASIA

The term myelodysplasia (MDS) refers to a group of bone marrow failure syndromes which are relatively rare in childhood. The pathogenesis of MDS is unknown, but a variety of chromosomal, molecular, and cytochem ical abnormalities have been reported. We describe a 4-month old femal e with MDS who presented with severe neutropenia and refractory anemia with excess blasts (RAEB). Bone marrow progenitor cell assays showed decreased erythroid and myeloid colony formation as compared to normal marrow, and the patient's serum further diminished colony formation o f both her own and control marrow. These observations suggested the pr esence of a soluble factor inhibitory to hematopoiesis. Reverse transc riptase-polymerase chain reaction (RT-PCR) analysis of total RNA deriv ed from the patient's bone marrow mononuclear cells revealed highly el evated tumor necrosis factor-alpha (TNF-alpha) mRNA levels. Using a si milar RT-PCR profile, TNF-alpha mRNA levels were found to be elevated in two other children with myelodysplasia. We conclude that TNF-alpha is produced in large amounts by bone marrow mononuclear cells or child ren with MDS, and we hypothesize that TNF-alpha plays an important rol e in the pathophysiology oi the ineffective hematopoiesis observed in MDS. (C) 1997 Wiley-Liss, Inc.