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Cancer Genetics
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Imbalance of DNA-dependent protein kinase subunits in polycythemia vera peripheral blood stem cells
Article first published online: 9 SEP 2008
DOI: 10.1002/ijc.23985
Copyright © 2008 Wiley-Liss, Inc.
Additional Information
How to Cite
Siebolts, U., Breuhahn, K., Hennecke, A., Schultze, J. L. and Wickenhauser, C. (2009), Imbalance of DNA-dependent protein kinase subunits in polycythemia vera peripheral blood stem cells. Int. J. Cancer, 124: 600–607. doi: 10.1002/ijc.23985
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Publication History
- Issue published online: 18 NOV 2008
- Article first published online: 9 SEP 2008
- Accepted manuscript online: 9 SEP 2008 12:00AM EST
- Manuscript Accepted: 4 AUG 2008
- Manuscript Received: 9 JAN 2008
Funded by
- The Cologne Fortune Foundation
- Center for Molecular Medicine
- University of Cologne (CMMC)
Keywords:
- polycythemia vera;
- CD34+;
- gene signature;
- DNA-PK;
- KU86
Abstract
Polycythemia vera (PV) is a clonal hematopoietic stem cell disease characterized by a trilinear accumulation of blood cells that has been recently associated with a JAK2V617F point mutation. However, this molecular defect represents a rather late event in the disease progression, is not specific for this disease, and is not ascertained in all patients indicating that additional factors contribute to the specific phenotype of PV. Therefore, cDNA microarray analyses were performed on CD34+ peripheral blood stem cells (PBSC) with subsequent evaluation on mRNA and protein level of a larger cohort of PV patients. Microarray analyses revealed a significant dysregulation of 11 genes. KU86, a gene coding for a subunit of the DNA-dependent protein kinase (DNA-PK), displayed the strongest upregulation in all patients under study. This peculiarity was accompanied by downregulation of the catalytic DNA-PK subunit DNA-PKcs. Also Ku86 protein was upregulated and expressed in the vast majority of CD34+ PBSC nuclei while a weak nuclear expression was detected in only one blood donor. Differential expression of several genes, imbalance of the distinct subunits of DNA-PK, and particularly the strong upregulation of Ku86 protein, are new findings in PV CD34+ PBSC. These factors may contribute to the accumulation of chromosomal aberrations, accumulation of hematopoietic cells (especially of erythropoiesis), and prolongation of CD34+ PBSC life span observed in PV. © 2008 Wiley-Liss, Inc.