c-Kit and c-kit mutations in mastocytosis and other hematological diseases.
Mast cells (MC) are tissue elements derived from hematopoietic stem cells. Their differentiation and proliferation processes are under the influence of cytokines, including one of utmost importance known as stem cell factor (SCF). SCF receptor is encoded by the protooncogene c-kit, belongs to the type III receptor tyrosine kinase subfamily, and is also expressed on other hematopoietic or non-hematopoietic cells. Ligation of c-kit receptor by SCF induces its dimerization, followed by induction of multiple intracellular signaling pathways leading to cell proliferation and activation. Mastocytosis, a relatively rare group of diseases characterized by accumulation of MC in various tissues, are found isolated or sometimes associated with other hematological malignancies in humans. Although the initial events leading to mastocytosis are not yet unraveled, alterations of the c-kit gene have been described. Particularly interesting are acquired mutations resulting in a constitutively activated receptor, possibly involved in the increased numbers of MC in tissues. For this reason, future strategies might be envisaged to target specifically the mutated c-kit and/or its intracellular signaling.
Boissan
M
M
Cellular and Molecular Hematology Unit, Faculty of Pharmacy, Paris, France.
Feger
F
F
Guillosson
J J
JJ
Arock
M
M
D019943:Amino Acid Substitution; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D019281:Dimerization; D006402:Hematologic Diseases / Q000235:genetics / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D008415:Mastocytosis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011519:Proto-Oncogenes; D051381:Rats; D017384:Sequence Deletion; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000502:physiology; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit