Induction by tumor-promoting phorbol diester of colony-stimulating activity in human myeloid leukemia cells transformed to macrophage-mimicking cells
Svet-Moldavskaya, I.A.; Arlin, Z.; Svet-Moldavsky, G.J.; Clarkson, B.D.; Koziner, B.; Mendelsohn, N.; Zinzar, S.N.; Holland, J.F.
Cancer Research 41(11 Pt 1): 4335-4340
1981
ISSN/ISBN: 0008-5472 PMID: 6975651 Document Number: 182200
The tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA), appears to induce a macrophage-mimicking transformation of cells in human promyelocytic leukemia continuous cultured lined HL-60, cells from normal human and chronic myeloid leukemia bone marrow, and cells from human acute leukemia bone marrow, and cells from human acute leukemias. Peripheral blood and/or bone marrow nucleated cells from 12 patients with acute myeloblastic leukemia (AML), 1 with acute promyelocytic leukemia (APL), 1 with acute myelomonocytic leukemia, 3 with myeloid blastic crisis of chronic myelogenous leukemia (Bl-CML), and 2 with acute lymphocytic leukemia (ALL) were exposed to TPA at concentrations from 10-7 to 10-9 M. After 1-4 days, in all cases except ALL, the cells acquired the peculiar morphology of macrophage-mimicking cells with multiple long or short thin pseudopods. TPA-untreated leukemic cells (HL-60, AML, APL, and Bl-CML) did not produce CSA [colony-stimulating activity]. All cells, whether treated with 10-8 M TPA or left untreated, did not produce CSA. No CSA was shown by lymphocyte-enriched normal human buffy coats treated with 10-8 M TPA. CSA production occurs in leukemic blasts treated with TPA themselves but not by some cellular minority present in leukemic blood and bone marrow buffy coats and possibly activated by TPA. TPA (10-8 M) itself incubated in culture medium without any cells up to 7 days did not possess any CSA. TPA is able not only to transform leukemic myeloid cells to macrophage-mimicking cells but also to induce CSA production by these cells.