生物谷報(bào)道：B細(xì)胞慢性淋巴細(xì)胞白血?。–LL）發(fā)病率相當(dāng)高,，但是在遺傳學(xué)背景上一直沒(méi)有找到與之對(duì)應(yīng)的基因突變或變異,。
由美國(guó)俄亥俄州立大學(xué)人類癌癥遺傳研究項(xiàng)目組Christoph Plass教授最近研究有明,，這種白血病,，可能與體一種死亡相關(guān)蛋白激酶1（DAPK1）活性下降有關(guān),。在發(fā)育過(guò)程中,，如果DAPK1基因出現(xiàn)沉默或不表達(dá)時(shí)，將明顯增加出生后的慢性淋巴細(xì)胞白血病,。而且通過(guò)對(duì)DAPK1基因的深入研究,，對(duì)CLL進(jìn)行了基因分型的研究，為將來(lái)個(gè)性化治療提供先期的探索,。
如果在受精時(shí),，DAPK1基因的活率如果在精子細(xì)胞中下降了75%，將在生長(zhǎng)發(fā)育過(guò)程中導(dǎo)致進(jìn)一步表達(dá)降低,，甚至失活,，從而大大增加患CLL的可能性,。當(dāng)然，目前仍然不知道DAPK1下降是因還是果,，需要更深和更廣泛的研究問(wèn)題,。
原始出處：
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.
原文鏈接：
Downregulation of Death-Associated Protein Kinase 1 (DAPK1) in Chronic Lymphocytic Leukemia.
Aparna Raval,1,10 Stephan M. Tanner,1 John C. Byrd,2 Elizabeth B. Angerman,1 James D. Perko,1 Shih-Shih Chen,1 Björn Hackanson,1,8 Michael R. Grever,2 David M. Lucas,2 Jennifer J. Matkovic,2 Thomas S. Lin,2 Thomas J. Kipps,6 Fiona Murray,7 Dennis Weisenburger,4 Warren Sanger,4 Jane Lynch,4 Patrice Watson,4 Mary Jansen,4 Yuko Yoshinaga,3 Richard Rosenquist,7 Pieter J. de Jong,3 Penny Coggill,5 Stephan Beck,5 Henry Lynch,4 Albert de la Chapelle,1,9, and Christoph Plass1
Cell, Vol 129, 879-890, 01 June 2007
