EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA-1 ON GROWTH AND APOPTOSIS OF HUMAN ACUTE MYELOGENOUS LEUKEMIA-CELLS

Because limited studies examined effects of transforming growth factor (TGF) beta1 on growth of human acute myelogenous leukemia (AML) cells, we used factor-dependent and primary AML cells to assess TGF-beta1 effects on human AML cell growth. OCI-AML1 cells were growth inhibited by TGF-beta1 regardless of which growth factor was used as a stimulus. In contrast, AML-193 cells were resistant to TGF-beta1 when grown with or without growth factors. UCSD/AML1 cells were sensitive to TGF-beta1 inhibition when grown with most cytokines but were relatively resistant to TGF-beta1 in the presence of macrophage colony-stimulating factor (M-CSF). Although cells grown from 5 of 6 AML patients were inhibited by TGF-beta1, cells from 1 AML patient were growth stimulated by TGF-beta1 in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF), M-CSF, or mast cell growth factor (kit ligand). Thus, 3 growth patterns with TGF-beta1 were observed: (a) sensitivity to growth inhibition; (b) resistance; and (c) factor-dependent resistance. Further studies showed that AML-193 and UCSD/AML1 cells expressed type II TGF-beta1 receptors and that ability of TGF-beta1 to decrease GM-CSF receptors did not correlate with growth inhibition. AML-193 cells and UCSD/AML1 cells grown with M-CSF could be propagated in 1 ng/ml TGF-beta1, but UCSD/AML1 cells grown with GM-CSF and TGF-beta1 died. Morphology and agarose gel analysis of DNA showed UCSD/AML1 cells underwent apoptosis when grown with GM-CSF and TGF-beta1 but not with M-CSF and TGF-beta1. Similar studies of OCI-AML1 cells showed that TGF-beta1 induced apoptosis of cells grown in 5637 bladder cell-conditioned medium or GM-CSF. These studies indicate that human AML cells exhibit heterogeneous growth responses to TGF-beta1 and that some effects of TGF-beta1 on myeloid cells occur through programmed cell death.