The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent inducer of differentiation, upon the in vitro proliferation of normal bone marrow and chronic myeloid leukemia granulocyte-macrophage progenitor cells were investigated in the presence or absence of exogenous colony-stimulating activity. In the absence of colony-stimulating activity, no colony formation occurred, whereas its presence was followed by the appearance of colonies almost exclusively composed of macrophagic cells. However, both normal and leukemic granulocytemacrophage progenitor cells showed a different response to TPA in terms of colony number and size. The number of colonies obtained from normal bone marrow was reduced to about 45% at three TPA concentrations (1 × 10-8, 1 × 10-10, and 1 × 10-12 m). By contrast, the plating efficiency of leukemic granulocyte-macrophage progenitor cells was not significantly affected by 1 × 10-10 and 1 × 10-12 m TPA, but was strongly reduced by 1 × 10-8 m. Moreover, TPA treatment did not significantly influence the size of colonies from normal bone marrow, while at 1 × 10-10 and 1 × 10-12 m, it remarkably increased that of the leukemic colonies. These different responses to TPA can be related to the abnormal sensitivity of chronic myeloid leukemia stem cells to factors regulating proliferation.
Supported by Grant CT80.00645.04 from Consiglio Nazionale delle Ricerche.