TCL1A and ATM are co-expressed in chronic lymphocytic leukemia cells without deletion of 11q

被引：3

作者：

Garding, Angela ^{[1
,2
]}

Bhattacharya, Nupur ^{[1
,3
]}

Haebe, Sarah ^{[1
]}

Mueller, Frederike ^{[4
]}

Weichenhan, Dieter ^{[5
]}

Idler, Irina ^{[1
]}

Ickstadt, Katja ^{[4
]}

Stilgenbauer, Stephan ^{[6
]}

Mertens, Daniel ^{[1
,6
]}

机构：

[1] Univ Ulm, DKFZ Heidelberg, Cooperat Unit Mech Leukemogenesis, D-89069 Ulm, Germany

[2] Inst Mol Biol, Mainz, Germany

[3] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[4] Tech Univ Dortmund, Dept Stat & Biometry, Dortmund, Germany

[5] DKFZ Heidelberg, Dept Epigen & Canc Risk Factors, Heidelberg, Germany

[6] Univ Ulm, Dept Internal Med 3, D-89069 Ulm, Germany

来源：

HAEMATOLOGICA | 2013年 / 98卷 / 02期

关键词：

KINASE-ACTIVITY; B-CELLS; EXPRESSION; METHYLATION; ACTIVATION; REGULATOR; SIGNALS;

D O I：

10.3324/haematol.2012.070623

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Chronic lymphocytic leukemia is characterized by the accumulation of B cells that are resistant to apoptosis. This resistance is induced by pro-survival stimuli from the microenvironment. TCL1 and ATM are central to the pathogenesis of the disease and associated with more aggressive disease. Their protein products have recently been shown to physically interact in leukemic cells and to impact on NF-kappa B signaling, which is a key regulator of apoptosis. In the present study we show that TCL1 and ATM are significantly co-expressed and up-regulated in malignant cells compared to non-malignant B cells, and that expression of TCL1 is partially deregulated by aberrant DNA-methylation. In addition, complex external stimuli induce essentially similar TCL1 and ATM time-course kinetics. In line with a coordinative regulation of NF-kappa B signaling by TCL1, its knockdown induced apoptosis in primary leukemia cells. These findings suggest that both genes functionally cooperate to modulate similar apoptosis-related cellular pathways.

引用

页码：269 / 273

页数：5