TCL1A and ATM are co-expressed in chronic lymphocytic leukemia cells without deletion of 11q
Angela Garding,
Nupur Bhattacharya,
Sarah Haebe,
Frederike Müller,
Dieter Weichenhan,
Irina Idler,
Katja Ickstadt,
Stephan Stilgenbauer,
Daniel Mertens
Affiliations
Angela Garding
Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany;Institute of Molecular Biology, Mainz, Germany
Nupur Bhattacharya
Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany;Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
Sarah Haebe
Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany
Frederike Müller
Department of Statistics and Biometry, Technical University Dortmund, Germany
Dieter Weichenhan
Department of Epigenomics and Cancer Risk Factors, DKFZ Heidelberg, Germany
Irina Idler
Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany
Katja Ickstadt
Department of Statistics and Biometry, Technical University Dortmund, Germany
Stephan Stilgenbauer
Department of Internal Medicine III, University Ulm, Germany
Daniel Mertens
Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany;Department 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.
