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Downregulation of d...
Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
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Raval, Aparna (author)
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Tanner, Stephan M. (author)
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Byrd, John C. (author)
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Angerman, Elizabeth B. (author)
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Perko, James D. (author)
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Chen, Shih-Shih (author)
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Hackanson, Björn (author)
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Grever, Michael R. (author)
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Lucas, David M. (author)
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Matkovic, Jennifer J. (author)
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Lin, Thomas S. (author)
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Kipps, Thomas J. (author)
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- Murray, Fiona (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Weisenburger, Dennis (author)
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Sanger, Warren (author)
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Lynch, Jane (author)
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Watson, Patrice (author)
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Jansen, Mary (author)
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Yoshinaga, Yuko (author)
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- Rosenquist, Richard (author)
- Uppsala universitet,Institutionen för genetik och patologi
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de Jong, Pieter J. (author)
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Coggill, Penny (author)
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Beck, Stephan (author)
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Lynch, Henry (author)
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de la Chapelle, Albert (author)
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Plass, Christoph (author)
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(creator_code:org_t)
- Elsevier BV, 2007
- 2007
- English.
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
Keyword
- HUMDISEASE
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Raval, Aparna
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Tanner, Stephan ...
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Byrd, John C.
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Angerman, Elizab ...
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Perko, James D.
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Chen, Shih-Shih
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show more...
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Hackanson, Björn
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Grever, Michael ...
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Lucas, David M.
-
Matkovic, Jennif ...
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Lin, Thomas S.
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Kipps, Thomas J.
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Murray, Fiona
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Weisenburger, De ...
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Sanger, Warren
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Lynch, Jane
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Watson, Patrice
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Jansen, Mary
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Yoshinaga, Yuko
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Rosenquist, Rich ...
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de Jong, Pieter ...
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Coggill, Penny
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Beck, Stephan
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Lynch, Henry
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de la Chapelle, ...
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Plass, Christoph
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show less...
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Cell
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Uppsala University