Colony-Stimulating Factor (CSF)-Dependent Growth of Two Leukemia Cell Lines

The progressive accumulation of leukemic cells in acute myeloblastic leukemia (AML) results from the self-renewal capacity of leukemic blast progenitors. The growth of leukemic blast progenitors is supported by growth factors and colony-stimulating factors (CSFs) have been shown to stimulate this phenomenon in vitro. After repeated subculture of leukemic cells obtained from a patient with AML M4 in the presence of recombinant G-CSF, a cell line dependent on G-CSF was established. This cell line, designated OCI/AMLla, does not respond to GM-CSF, interleukin-3 (IL-3), IL-1 or stem cell factor as well as G-CSF. The stimulatory effect of G-CSF on OCI/AMLla cells is almost completely blocked by monoclonal anti-G-CSF antibody. With G-CSF added in the culture, the OCI/AMLla cell line has been growing exponentially for over 5 years now.

Another cell line, with growth dependent on IL-3, has also been established from a patient with chronic lymphocytic leukemia in the acute phase. This cell line TMD2 does not respond to G-CSF, GM-CSF, IL-1, or stem cell factor and anti-IL-3-antibody blocks the stimulatory effect of IL-3 on these cells. Receptors for IL-3 have been found on the surface of TMD2 cells. Although the TMD2 cell line is not derived from AML, the novel character of IL-3-dependency provides useful information for the study of the role of growth factor(s) in leukemic cell proliferation. These two CSF-dependent cell lines are expected to be excellent models for the investigation of the precise mechanism by which G-CSF and IL-3 stimulate the growth of leukemic cells.