Expression and functional role of the proto-oncogene c-kit in acute myeloblastic leukemia cells

作者：Hiroya Ikeda, Y Kanakura, Tomoko Tamaki, Akira Kuriu, H. Kitayama, Jun Ishikawa, Y Kanayama, Takayuki Yonezawa, Seiichiro Tarui, JD Griffin · 发表于：Blood · 年份：1991 · DOI：10.1182/blood.v78.11.2962.2962 · 被引用次数：270 · 研究领域：Acute Myeloid Leukemia Research、Multiple Myeloma Research and Treatments、Chronic Myeloid Leukemia Treatments

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.