Expression, function and activation of the proto-oncogene c-kit product in human leukemia cells.
The c-kit proto-oncogene encodes a receptor tyrosine kinase that is considered to play important roles in hematopoiesis. The proto-oncogene c-kit product is expressed on various types of human cell lines derived from leukemic cells of erythroid, megakaryocytic and mast-cell lineages. Also, the c-kit product is detectable in blast cells in most cases of acute myeloblastic leukemia (AML) and in some cases of chronic myelogenous leukemia (CML) in blastic crisis (BC). By contrast, little or no expression of c-kit is observed in human leukemia cell lines of lymphoid lineage and in blast cells in acute lymphoblastic leukemia (ALL). Tyrosine phosphorylation and activation of the c-kit product with the ligand for c-kit (stem cell factor: SCF) results in proliferation of some human leukemia cell lines, such as M07E, and blast cells in a substantial fraction of AML cases. In addition, SCF appears to have an activity in inducing differentiation of certain types of leukemic cells. In some cases, further, the c-kit product is found to be activated in leukemic cells even before the stimulation with SCF. These results suggest that c-kit may be involved in excessive proliferation and aberrant differentiation of human leukemia cells.
Kanakura
Y
Y
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Ikeda
H
H
Kitayama
H
H
Sugahara
H
H
Furitsu
T
T
D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit