| Summary: | 碩士 === 臺北醫學大學 === 醫學科學研究所 === 96 === Chronic myeloid leukemia (CML) is a clnal bone marrow stem cell disorder. Majority of CML patients have the Philadelphia (Ph) chromosome, a consequence of translocation between chromosomes 9 and 22. The Ph chromosome generates the Bcr-Abl fusion gene, which encodes the Bcr-Abl protein with a constitutive tyrosine kinase activity. Bcr-Abl activate multiple signalings pathways and is the main determinant of the CML cell malignant phenotype,including increased cell proliferation, inhibited apoptosis and differentiation. We have previously shown that CD69 is expressed in the CML cell line-K562 cells. In this study, we investigate whether CD69 is the downstream target of Bcr-Abl and the CD69 functions in CML cells. We found that Bcr-Abl upregulated CD69 promoter activity through MEK pathway and NF-κB pathway in Bcr-Abl overexpressing cells. Transient transfection assay indicated that Bcr-Abl upregulated CD69 promoter may be through NF-κB (p65) or AP-1 transcription factor “c-Jun.”The expression level of CD69 protein was also increased in p65 or c-Jun overexpressing cells. To investigate CD69 function in CML cells, we used CD69 monoclonal antibody to crosslink CD69 in K562 cells stably overexpressing CD69.Our results indicated that CD69 overexpression up-regulate tyrosine phosphrylated signals in K562. Then, more tyrosine phosphrylated signals were increased after CD69 cross-linking .STI571 is an inhibitor of Abl tyrosine kinase and has been proven to be effective for CML patients. After treatment with STI571, CD69 partially increased K562 cells viability and decreases apoptotic cells with or without CD69 cross-linking. STI571 and Activin A both induced human erythroid differentiation. Here we show that after treatment with STI571 or Activin A, CD69 partially inhibits K562 cell differentiation with or without CD69 cross-linking. In conclusion, CD69 is involved in Bcr-Abl signaling to increase cell proliferation and inhibit cell apoptosis and differentiation in CML cell.
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