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Expression and functional role of the proto-oncogene c-kit in acute
myeloblastic leukemia cells
H Ikeda, Y Kanakura, T Tamaki, A Kuriu, H Kitayama, J Ishikawa, Y Kanayama, T Yonezawa, S Tarui and JD Griffin
Second Department of Internal Medicine, Osaka University Medical School,
Japan.
The c-kit proto-oncogene encodes a receptor tyrosine kinase that is thought
to play an important role in hematopoiesis. In a series of human acute
myeloblastic leukemia (AML), the expression of the c-kit proto-oncogene and
its product was studied by means of Northern blot and immunoblot analyses.
The c-kit mRNA was expressed in 20 of 25 cases of AML, and in those cases
the product of the c-kit proto-oncogene was detected by immunoblotting with
anti-c-kit antibody. The expression of c-kit transcripts and protein was
barely detectable in normal bone marrow cells as a control. The expression
of c-kit transcript did not correlate with the French-American-British
classification nor clinical manifestations. In 6 of 11 cases that expressed
c-kit product, AML cells were found to proliferate in response to
recombinant human stem cell factor (rhSCF), the ligand for c-kit, and the
synergistic stimulation of AML cells was observed by rhSCF and granulocyte-
macrophage colony-stimulating factor. Immunoblotting with anti-
phosphotyrosine antibody showed that the c-kit receptor protein was
detectably phosphorylated in 7 of 12 cases tested before the stimulation
with rhSCF, while the rhSCF treatment resulted in an increased tyrosine
phosphorylation of c-kit in AML cells. These results indicate that c-kit
proto-oncogene is expressed in most cases of AML and is functional in terms
of supporting proliferation.
Volume 78,
Issue 11,
pp. 2962-2968,
12/01/1991
Copyright © 1991 by The American Society of Hematology
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