Role of Hemopoietic Growth Factors inn the Proliferation of Acute Myeloid Leukemia

Selective growth advantage of the leukemic clone over normal populations can either result from growth factor independency or, on the opposite, from an increased cell response to haemopoietic growth factors. In order to define the relationship between growth factors and leukemic cell proliferation, we studied the growth patterns of 44 Acute Myeloid Leukemia (AML) cell samples in vitro, with or without exogenous growth factors. As spontaneous proliferation was observed in 64% of the cases, growth factor gene expression and secretion of the factor in the culture medium were studied in some of these specimens. Primary AML cells were found to express several growth factor genes: IL-lα and β, GM-CSF, CSF -1, and sometimes G-CSF and IL-6. Protein excretion in the culture supernatant was documented for GM-CSF, CSF-1 and IL-lα using specific functional assays. AML cells were shown to respond by an induction or an amplification of their proliferation to the addition of human recombinant IL-3, GM-CSF and G-CSF. The existence of an autocrine loop involving GM-CSF gene expression, excretion of the protein and inhibition by specific antibodies was demonstrated in some AML with high indexes of in vitro proliferation. These results suggest that haemopoietic growth factors play a major role in the proliferation of AML cells, since these cells are able to synthesize and to respond to the major CSF or Interleukins involved in normal haemopoiesis.