Growth regulation of malignant clonogenic cells in acute myeloid leukemia.
Myeloid leukemic progenitor cells proliferate in vitro in response to a variety of humoral factors, the most prominent among these being granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism by which GM-CSF transduces its proliferative signal in acute myeloid leukemia has been extensively investigated over the past year. It is now known that the GM-CSF belongs to a new family of hematopoietic growth factor binding proteins which are characterized by a relatively short intracytoplasmic domain that lacks a tyrosine kinase sequence. Nevertheless, studies performed using GM-CSF-dependent leukemic cell lines demonstrate the appearance of several new phosphotyrosine species after GM-CSF exposure, suggesting that receptor activation is directly or indirectly linked to tyrosine kinase stimulation. Apart from the basic biology of GM-CSF-induced signal transduction, the ability of this factor to enhance the S-phase fraction of myeloid leukemia blasts may have important therapeutic implications. Clinical trials are currently being conducted in an attempt to determine whether GM-CSF is able to overcome kinetic resistance of leukemic myeloblasts to cell cycle-specific agents such as cytarabine in the treatment of patients with acute myeloid leukemia.
Cannistra
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Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
D002999:Clone Cells / Q000473:pathology; D003115:Colony-Stimulating Factors / Q000502:physiology; D016207:Cytokines / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D003115:Colony-Stimulating Factors; D016207:Cytokines; D009363:Neoplasm Proteins; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins