Spontaneous Growth of Chronic Myelomonocytic Leukemia Cells

We studied the effects ofIL4 on the spontaneous proliferation of chronic myelomonocytic leukemia (CMMoL) cells in vitro. ILA (100 U/ml) suppressed the spontaneous DNA synthesis by 50% in 5 of 8 cases examined. 1L4 (100 U/ml) also inhibited the spontaneous colony formation by CMMoL cells in a methylceliulose culture by 50-97% in all of the 10 cases in which spontaneous colonies were formed. This IL4-mediated suppression of the growth of CMMoL cells was completely abolished by the addition of anti-IL4 neutralizing antibodies. The spontaneous CMMoL colonies were substantially suppressed by the addition of either anti-IL-6 or anti-granulocyte/ macrophage colony-stimulating factor (GM-CSF) antibodies to the colony assay system: the addition of both anti-IL-6 and anti-GM-CSF antibodies resulted in > 80% inhibition of the colony formation byCMMoL cells. On the other hand, none of anti-IL-1-#, anti-granulocyte-CSF, anti-macrophage-CSF, or anti-tumor necrosis factorantibodies affected the CMMoL colony formation. In the supernatants from 24-h cultures of CMMoL cells, high levels of IL-6 and GM-CSF were demonstrated in 9 of 9 and 2 of 9 cases examined, respectively. IL4 (100 U/ml) almost completely inhibited the secretion of IL-6 and GM-CSF by CMMoL cells. These observations suggest that I14 suppresses the spontaneous proliferation ofCMMoL cells by inhibiting their production of IL-6 and/or GM-CSF, both of which could act in vitro as an autocrine growth factor for CMMoL cells. (J. Clin. Invest. 1991.88:223-230.)