@article{b9ccd90c6f9046148237c74166c2833f,
title = "Downregulation of Death-Associated Protein Kinase 1 (DAPK1) in Chronic Lymphocytic Leukemia",
abstract = "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.",
keywords = "HUMDISEASE",
author = "Aparna Raval and Tanner, {Stephan M.} and Byrd, {John C.} and Angerman, {Elizabeth B.} and Perko, {James D.} and Chen, {Shih Shih} and Bj{\"o}rn Hackanson and Grever, {Michael R.} and Lucas, {David M.} and Matkovic, {Jennifer J.} and Lin, {Thomas S.} and Kipps, {Thomas J.} and Fiona Murray and Dennis Weisenburger and Warren Sanger and Jane Lynch and Patrice Watson and Mary Jansen and Yuko Yoshinaga and Richard Rosenquist and {de Jong}, {Pieter J.} and Penny Coggill and Stephan Beck and Henry Lynch and {de la Chapelle}, Albert and Christoph Plass",
note = "Funding Information: The authors wish to thank all members of the Plass and Byrd labs for critical discussions; Mattias Jansson from Uppsala University: and the Sequencing Division at the Wellcome Trust Sanger Institute for excellent technical assistance: Ramana Davuluri, Sandya Liyanarachchi, and Greg Singer for statistical support; Nickolas Papadopoulos for the conversion to haploidy; and Paivi Lahermo of the Finnish Genome Center for genotyping and linkage analyses. A.R. is supported by a T32 CA106196 fellowship in Cancer Genetics. B.H. is supported by a grant from the Dr. Mildred Scheel Foundation for Cancer Research, Germany. This publication was supported by National Cancer Institute grants CA110496 (J.C.B., C.P., and A.R.), CA101956 (C.P. and J.C.B.) CA81534 to the CLL Research Consortium (J.C.B., M.G., and T.J.K.), P30 CA16058 (A.d.l.C., C.P., and J.C.B.), The Leukemia and Lymphoma Society of America (J.C.B. and C.P.), and the D. Warren Brown Foundation (J.C.B. and C.P.). Further support came from revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services (NDHHS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the state of Nebraska or NDHHS. Support was also received by NIH grant 5U01 CA86389 and the Swedish Cancer Society. C.P. is a Leukemia and Lymphoma Society scholar, and J.C.B. is a Leukemia and Lymphoma Society clinical scholar. P.C. and S.B. were supported by the Wellcome Trust. ",
year = "2007",
month = jun,
day = "1",
doi = "10.1016/j.cell.2007.03.043",
language = "English (US)",
volume = "129",
pages = "879--890",
journal = "Cell",
issn = "0092-8674",
publisher = "Elsevier B.V.",
number = "5",
}