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Effects of Transforming Growth Factor ß1 on Growth and Apoptosis of Human Acute Myelogenous Leukemia Cells¹

Departments of Medicine and Pathology, Arizona Health Sciences Center, and Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724 [R. T., C. P., B. D. S., M. R.]; and Celtrix Pharmaceuticals, Inc., Santa Clara, California 94052 [P. S.]

Because limited studies examined effects of transforming growth factor (TGF) ß1 on growth of human acute myelogenous leukemia (AML) cells, we used factor-dependent and primary AML cells to assess TGF-ß1 effects on human AML cell growth. OCI-AML1 cells were growth inhibited by TGF-ß1 regardless of which growth factor was used as a stimulus. In contrast, AML-193 cells were resistant to TGF-ß1 when grown with or without growth factors. UCSD/AML1 cells were sensitive to TGF-ß1 inhibition when grown with most cytokines but were relatively resistant to TGF-ß1 in the presence of macrophage colony-stimulating factor (M-CSF). Although cells grown from 5 of 6 AML patients were inhibited by TGF-ß1, cells from 1 AML patient were growth stimulated by TGF-ß1 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-ß1 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-ß1 receptors and that ability of TGF-ß1 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-ß1, but UCSD/AML1 cells grown with GM-CSF and TGF-ß1 died. Morphology and agarose gel analysis of DNA showed UCSD/AML1 cells underwent apoptosis when grown with GM-CSF and TGF-ß1 but not with M-CSF and TGF-ß1. Similar studies of OCI-AML1 cells showed that TGF-ß1 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-ß1 and that some effects of TGF-ß1 on myeloid cells occur through programmed cell death.

¹ This work supported in part by NIH National Cancer Institute Grants CA32094 and CA23074.

² To whom requests for reprints should be addressed, at 1515 N. Campbell Ave., Tucson, AZ 85724.

Received 12/ 7/92. Accepted 5/11/93.

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