- Angela Garding1,2,
- Nupur Bhattacharya1,3,
- Sarah Haebe1,
- Frederike Müller4,
- Dieter Weichenhan5,
- Irina Idler1,
- Katja Ickstadt4,
- Stephan Stilgenbauer6 and
- Daniel Mertens1,6⇓
- 1Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany
- 2Institute of Molecular Biology, Mainz, Germany
- 3Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
- 4Department of Statistics and Biometry, Technical University Dortmund, Germany
- 5Department of Epigenomics and Cancer Risk Factors, DKFZ Heidelberg, Germany
- 6Department of Internal Medicine III, University Ulm, Germany
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-κB 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-κB 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.
Authorship and Disclosures: Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at www.haematologica.org.
- Received May 24, 2012.
- Accepted July 18, 2012.
- ©2013 Ferrata Storti Foundation