Induction by tumor-promoting phorbol diester of colony-stimulating activity in human myeloid leukemia cells transformed to macrophage-mimicking cells

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 leukemias. In the present experiments, 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 (BI-CML), and 2 with acute lymphocytic leukemia (ALL) were exposed to TPA at concentrations from 10 super(-7) to 10 super(-9) m. After 1 to 4 days, in all cases except ALL, the cells acquired the peculiar morphology of macrophage-mimicking cells with multiple long or short thin pseudopods. These experiments show that TPA is able not only to transform leukemic myeloid cells to macrophage-mimicking cells but also to induce CSA production by these cells.