CELL-PROLIFERATION AND DIFFERENTIATION IN CHEMICAL LEUKEMOGENESIS

In tissues such as bone marrow with normally high rates of cell divisi on, proliferation is tightly coordinated with cell differentiation. Su rvival, proliferation and differentiation of early hematopoietic proge nitor cells depend on the growth factors, interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF) and their sy nergism with other cytokines. We provide evidence that a characteristi c shared by a diverse group of compounds with demonstrated leukemogeni c potential is the ability to act synergistically with GM-CSF. This re sults in an increase in recruitment of a resting population of hematop oietic progenitor cells normally unresponsive to the cytokine and a tw ofold increase in the size of the proliferating cell population normal ly regarded to be at risk of transformation in leukemogenesis. These f indings support the possibility that transient alterations in hematopo ietic progenitor cell differentiation may be an important factor in th e early stages of development of leukemia secondary to chemical or dru g exposure.