Effects of transforming growth factor beta, tumor necrosis factor alpha, interferon gamma and LIF-HILDA on the proliferation of acute myeloid leukemia cells.
A group of polypeptide factors that regulate cell growth and differentiation has been tested for their biological activities on the growth and differentiation of leukemic cells isolated from patients with Acute Myeloid Leukemias (AML). The effects of Transforming Growth Factor beta 1 (TGF beta), Tumor Necrosis Factor alpha (TNF alpha), Interferon gamma (IFN gamma) and LIF-HILDA were compared on leukemic cells cultured in vitro for seven days. Spontaneously growing leukemic cells were selected in order to study either inhibition or enhancement of proliferation induced by these factors. Only TGF beta 1 was found to induce a clear inhibition of leukemic proliferation in all cases tested. Recombinant TNF alpha and IFN gamma were found to induce either inhibition or enhancement of the proliferation on separate specimens. Under the conditions of culture, it was not possible to document any effect of LIF-HILDA. Cell differentiation and cell maturation were documented studying the modulation of cell surface antigens. TGF beta did not modify antigen expression on the cells surviving after 3 days in culture. Both TNF alpha and IFN gamma were found to enhance the expression of adhesion molecules and to a lesser extent, the expression of some lineage associated antigens. No effect of LIF-HILDA on antigen modulation was documented in the cases tested. These data confirm that TGF beta is by itself a potent inhibitor of the myeloid leukemia cells proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
Kerangueven
F
F
INSERM U.119, Marseille, France.
Sempere
C
C
Tabilio
A
A
Mannoni
P
P
D000951:Antigens, Neoplasm / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006131:Growth Inhibitors; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D007948:Leukemia, Monocytic, Acute / Q000473:pathology*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D015479:Leukemia, Myelomonocytic, Acute / Q000473:pathology*; D008222:Lymphokines / Q000494:pharmacology*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor