Modulation of responsiveness of chronic myelogenous leukemia granulocyte-macrophage colony-forming cells to growth regulation following in vivo treatment with recombinant gamma-interferon.
A patient with Philadelphia chromosome (Ph) chronic myelogenous leukemia (CML), in chronic phase, was treated with recombinant gamma-interferon (r gamma-IFN) in a phase I clinical trial. Prior to treatment, analysis of in vitro agar culture parameters indicated hyporesponsiveness of granulocyte-macrophage colony-forming cells (CFU-GM) to inhibition by prostaglandin E and acidic isoferritins and diminished expression of class II major histocompatibility complex (MHC) antigens (HLA-DR). Treatment was associated with no change in bone marrow cellularity or in the percentage of Ph cells. However, in vitro cultures of bone marrow cells showed a return to normal levels of both expression of CFU-GM class II antigen and of sensitivity to inhibition by prostaglandin E and acidic isoferritins which predicted and/or confirmed clinical response. Throughout the course of interferon therapy, white blood cell counts (WBC) and the percentage of bone marrow blast cells were maintained at normal levels. Onset of aggressive-phase disease was associated with increased WBC, an increase in bone marrow blast cells, a secondary chromosomal abnormality, loss of CFU-GM sensitivity to inhibition by putative negative growth regulators, and markedly diminished MHC class II antigen expression. Following a bone marrow transplant from a matched sibling, all hematologic parameters studied were found to be normal. These findings indicate that treatment with r gamma-IFN can modulate some of the abnormal growth characteristics of CFU-GM observed in CML.
D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D005260:Female; D006098:Granulocytes / Q000473:pathology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use
D011994:Recombinant Proteins; D007371:Interferon-gamma