Study of differentiation of fresh myelogenous leukemic cells by compounds that induce a human promyelocytic leukemic line (HL-60) to differentiate.
The human promyelocytic leukemia cell line known as HL-60 can be triggered to mature to functional granulocytes and/or macrophages after exposure to a variety of compounds. The findings have generated enthusiasm for possible therapy of leukemia using compounds that induce leukemic cell differentiation. We investigated whether five compounds known to trigger HL-60 differentiation to granulocytes could trigger the maturation of blast cells from 12 patients with myelogenous leukemia. Maturation was judged by morphology, superoxide production, phagocytosis, expression of Fc receptors, and development of alpha-napthyl acetate esterase activity. The blast cells from most patients showed little morphological, histological or functional maturation after exposure to the various compounds as compared to the blast cells cultured without the compounds. Actinomycin was able to induce significant maturation of leukemic cells of some patients when maturation was analyzed by several statistical methods. Our study suggests that many compounds which trigger differentiation of promyelocytic leukemia cells may not trigger differentiation of less mature myeloid leukemic cells.
D000328:Adult; D000368:Aged; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003609:Dactinomycin / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008875:Middle Aged; D009580:Nitroblue Tetrazolium / Q000378:metabolism; D010587:Phagocytosis; D013866:Thioguanine / Q000494:pharmacology
D007042:Hypoxanthines; D003609:Dactinomycin; D009580:Nitroblue Tetrazolium; D019271:Hypoxanthine; D013866:Thioguanine; D004121:Dimethyl Sulfoxide