The presence of Ia-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in normals and patients with chronic myeloid leukemia. Consistent reduction of normal colony formation to approximately 50% of baseline levels was observed using a monoclonal anti-human Ia antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. Elimination of the Ia-antigen-bearing CFU-GM population was associated with virtually a complete loss of responsiveness to the inhibitory effects of prostaglandin E. Maintenance of bone marrow cells in short-term suspension culture at 37°C prior to agar culture resulted in the loss of detectable Ia-antigen on the CFU-GM and, similarly, loss of response to prostaglandin. In contrast, most patients with chronic myeloid leukemia showed greatly reduced levels of Ia-antigens on their CFU-GM in fresh marrow together with lack of prostaglandin sensitivity, suggesting a correlation with the abnormal growth regulation observed in these patients. In two chronic myeloid leukemia patients, levels of Ia-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggst a relationship in normals between the expression of Ia-antigens on CFU-GM and the physiologic response to regulation by prostaglandin E, and a possible mechanism for the aberrant regulatory response in patients with chronic myeloid leukemia.
ASJC Scopus subject areas
- Cell Biology