Restoration of responsiveness of chronic myeloid leukemia granulocyte-macrophage colony-forming cells to growth regulation in vitro following preincubation with prostaglandin E.
The ability to modulate granulocyte-macrophage colony-forming unit (CFU-GM) Ia-antigen expression and response to growth inhibition in vitro was investigated in normals and patients with chronic myeloid leukemia (CML). The hyporesponsiveness of CML CFU-GM to inhibition by prostaglandin E and acidic isoferritins in vitro and their associated diminished capacity for Ia-antigen expression could be reversed following suspension culture of bone marrow cells in the presence of prostaglandin E prior to soft agar culture. Suspension preculture with prostaglandin E for 24 hr resulted in the detection of a population of CFU-GM that were equivalent to normal CFU-GM in both response to inhibition by prostaglandin E and acid isoferritins and in their pattern of Ia-antigen expression. Cytogenetic analysis of the progeny of CFU-GM proliferating in cultures established from marrow cells, cultured directly upon isolation or following suspension culture in the absence or presence of prostaglandin E for 24 hr, indicated that the responding cell population belonged to the Ph1-positive leukemic clone. Antigen detection on these CFU-GM resulted both from Ia-antigen reexpression and the induction of noncycling cells into S-phase with coincident expression of Ia-antigens. These studies provide further evidence for a direct regulatory association between Ia-antigen and control of granulocyte-macrophage progenitor cell proliferation, offer a possible explanation for the disordered regulatory responses observed in patients with CML, and indicate that abnormal growth phenotypes can be modulated, at least in vitro.
D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005293:Ferritins / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007951:Leukemia, Myeloid / Q000097:blood*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology*
D006131:Growth Inhibitors; D006649:Histocompatibility Antigens; D011458:Prostaglandins E; D005293:Ferritins