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  • 1
    Publication Date: 1983-07-01
    Description: 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.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 1982-02-01
    Description: The presence of la-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in animals 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 la antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. ELimination of the la-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 degrees C prior to agar culture resulted in the loss of detectable la-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 la-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 la-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggest a relationship in normals between the expression of la-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.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 1982-02-01
    Description: The presence of la-antigens and their relationship to the inhibitory effect of prostaglandin E on the proliferation of human CFU-GM was studied in animals 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 la antibody in a complement-dependent cytotoxicity assay titrated over serial dilutions. ELimination of the la-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 degrees C prior to agar culture resulted in the loss of detectable la-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 la-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 la-antigen higher than that observed in the majority of patients could be detected and correlated with a residual response to prostaglandin E. These results suggest a relationship in normals between the expression of la-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.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 1983-07-01
    Description: 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.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
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