Journal
BLOOD CELLS MOLECULES AND DISEASES
Volume 55, Issue 4, Pages 373-381Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bcmd.2015.08.002
Keywords
CD34(+) cells; Granulocytes; Chronic myeloid leukemia; Microarray analysis
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Funding
- Intramural Research Program of Alan N. Schechter at the National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda [Z01 DK025016-33]
- Serbian Ministry of Education, Science and Technological Development [175053]
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Purpose: We compared the gene expression profile of peripheral blood CD34(+) cells and granulocytes in subjects with chronic myeloid leukemia (CML), with the accent on signaling pathways affected by BCR-ABL oncogene. Methods: The microarray analyses have been performed in circulating CD34(+) cells and granulocytes from peripheral blood of 7 subjects with CML and 7 healthy donors. All studied BCR-ABL positive CML patients were in chronic phase, with a mean value of 2012 +/- SD of CD34(+) cells/mu l in peripheral blood. Results: The gene expression profile was more prominent in CML CD34(+) cells (3553 genes) compared to granulocytes (2701 genes). The 41 and 39 genes were significantly upregulated in CML CD34(+) cells (HINT1, TXN, SERBP1) and granulocytes, respectively. BCR-ABL oncogene activated PI3K/AKT and MAPK signaling through significant upregulation of PTPN11, CDK4/6, and MYC and reduction of E2F1, KRAS, and NFKBIA gene expression in CD34(+) cells. Among genes linked to the inhibition of cellular proliferation by BCR-ABL inhibitor Imatinib, the FOS and STAT1 demonstrated significantly decreased expression in CML. Conclusion: The presence of BCR-ABL fusion gene doubled the expression quantity of genes involved in the regulation of cell cycle, proliferation and apoptosis of CD34(+) cells. These results determined the modified genes in PI3K/AKT and MAPK signaling of CML subjects. (C) 2015 Elsevier Inc. All rights reserved.
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