Hematopoietic Growth Factors and Blast Progenitors in Acute Leukemia

Leukemic cells are maintained by a minor subpopulation of cells called leukemic stem cells (LSC) with proliferative and self-renewal capacity, both of which are detected with leukemic colony assay, with the latter being an important prognositic factor. Drug sensitivity tests employing leukemic colony assay revealed the effects of cytotoxic drugs on LSC to be diverse and that cytosine arabinoside predominantly suppresses self-renewal, which probably accounts for its effectiveness in AML therapy. Hematopoietic growth factors (HGFs) regulate the growth of LSC and various in vitro effects of HGFs on acute leukemia cells have been reported. These effects appear to reflect physiological functions of each HGF and can be categorized into groups according to their distinct functions. Endogenously produced HGFs stimulate LSC in an autocrine or a paracrine fashion, resulting in autonomous growth of these cells, which also correlates with the patients' prognosis. HGFs can enhance the cytotoxicity of anti-leukemia drugs in vitro, possibly mainly through recruitment of LSC from the dormant state into active cell cycling. HGFs have been clinically tested in leukemia therapy. Although recovery of blood leukocyte counts can consistently be accelerated with HGF treatment, the effectiveness of HGFs in sensitizing leukemia cells to chemotherapeutic agents and/or improving patient prognosis has not been clearly demonstrated. Different strategies using HGFs and related molecules must be tested in future leukemia therapy.