Heterogeneity of Ia antigen expression by proliferating nonlymphocytic leukemia blast cells.
In vitro systems were used to detect Ia-like antigens on proliferating normal myeloid and acute nonlymphocytic leukemia (ANLL) blast cells. Incubation of normal bone marrow cells with a monoclonal anti-Ia antibody and complement resulted in toxicity for both granulocyte/macrophage progenitors (CFU-GM) (toxicity 79%-100%) and cells proliferating in liquid culture in response to placenta-conditioned medium colony-stimulating factor (CSF) or medium conditioned by normal, phytohemagglutinin (PHA)-stimulated mononuclear cells. In contrast, effects of anti-Ia antibody and complement on blast colony-forming cells and 3H-TdR incorporation in liquid culture from eight patients with ANLL were variable. Colony growth with CSF after treatment was 0% to 91% of control growth and did not correlate with display of Ia-like antigens. Survival of ANLL cells growing in liquid cultures was even more variable after anti-Ia+ complement treatment (28%-227% of control). The presence of Ia-like antigens did not distinguish ANLL cells responding to PHA-conditioned medium from those responding to CSF in either colony or liquid culture. Dose-response curves for ANLL cells in liquid culture were similar before and after treatment with anti-Ia+ complement. In contrast to normal myeloid precursor cells, which show uniform display of Ia-like antigens, display of Ia antigen by proliferating leukemia cells is highly variable from patient to patient. Anti-Ia reagents such as this one would not be effective in treating ANLL marrow for autologous transplantation.
D000208:Acute Disease; D000911:Antibodies, Monoclonal; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003115:Colony-Stimulating Factors; D003165:Complement System Proteins; D003470:Culture Media; D003602:Cytotoxicity, Immunologic; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007938:Leukemia / Q000276:immunology* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000276:immunology; D014410:Tumor Stem Cell Assay
D000911:Antibodies, Monoclonal; D003115:Colony-Stimulating Factors; D003470:Culture Media; D000949:Histocompatibility Antigens Class II; D003165:Complement System Proteins