Abnormal Responsiveness of Granulocyte-Macrophage Committed Colonyforming Cells from Patients with Chronic Myeloid Leukemia to Inhibition by Prostaglandin E
Abstract
The formation of myeloid colonies in soft-agar cultures of normal human marrow was markedly inhibited by prostaglandin E. Morphological characterization of colonies in the presence or absence of prostaglandin E 1 showed that inhibition was restricted to monocytoid rather than neutrophil differentiation. Myeloid colony formation by granulocyte-macrophage-committed colony-forming cells from patients with chronic myeloid leukemia was not inhibited even by high concentrations of prostaglandin E and was independent of colony morphology. The altered sensitivity of leukemic colony-forming cells to prostaglandin E was observed at all stages of the disease and persisted following chemotherapy-induced reversion to a partial or complete Philadelphia chromosome-negative bone marrow status. This evidence suggests that altered myeloid stem cell sensitivity to a normal regulatory factor may play a role in the pathophysiology of chronic myeloid leukemia. 1 Supported by Grants CA-08748, CA-23528, and CA-20194, and the Gar Reichman Foundation. 2 Recipient of National Service Award F32-CA-05904 from the National Cancer Institute, Department of Health, Education, and Welfare. Special fellow of The Leukemia Society of America. To whom requests for reprints should be addressed, at Department of Developmental Hematopoiesis, Sloan-Kettering Institute for Cancer Research, 1250 First Avenue, New York, N. Y. 10021. 3 Scholar of the Leukemia Society of America.