Production of human pluripotent progenitor cell colony stimulating activity (CFU-GEMM CSA) in patients with myelodysplastic syndromes

Abstract

The present study was aimed at assessing the possible relationship between the T-lymphocyte abnormalities and the stem cell dysfunction in myelodysplastic syndromes (MDS), by investigating the production of specific stimulators of stem cell differentiation in such patients. Conditioned media from peripheral blood mononuclear cells (PBMNC) of MDS patients and healthy controls, prepared with or without phytohaemagglutinin (PHA), were assayed for their capacity to stimulate the in-vitro formation of multilineage colonies (CFU-GEMM) in target marrow cell cultures of healthy donors. Both PHA-induced DNA synthesis and T-cell subpopulation ratios (T 4/T 8) in patient cells were significantly lower than in controls. However, no impaired production of pluripotent progenitor cell colony stimulating activity (CFU-GEMM CSA) by PHA-stimulated and unstimulated PBMNC, could be found. Normal levels of activity were also produced by isolated T lymphocytes of MDS patients. Autologous serum neither enhanced nor suppressed the production of CFU-GEMM CSA. Our observations demonstrate that PHA-induced production of CFU-GEMM CSA is not directly correlated with DNA synthesis. Furthermore, we have found that both major T-cell subsets, defined by OKT4 and OKT8 monoclonal antibodies, are equally capable of producing CFU-GEMM CSA. The normal production of CFU-GEMM CSA by T cells of MDS patients suggests that this T-cell function is not an etiological factor in the stem cell disorder of myelodysplastic syndromes.