title: TCL1A and ATM are co-expressed in chronic lymphocytic leukemia cells without deletion of 11q.
abstract: 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.
authors.affiliation: Cooperation Unit Mechanisms of Leukemogenesis, University Ulm, DKFZ Heidelberg, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Garding
authors.forename: Nupur
authors.initials: N
authors.lastname: Bhattacharya
authors.forename: Sarah
authors.initials: S
authors.lastname: Haebe
authors.forename: Frederike
authors.initials: F
authors.lastname: Müller
authors.forename: Dieter
authors.initials: D
authors.lastname: Weichenhan
authors.forename: Irina
authors.initials: I
authors.lastname: Idler
authors.forename: Katja
authors.initials: K
authors.lastname: Ickstadt
authors.forename: Stephan
authors.initials: S
authors.lastname: Stilgenbauer
authors.forename: Daniel
authors.initials: D
authors.lastname: Mertens
mesh_terms: D000328:Adult; D000368:Aged; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11; D005260:Female; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; D064007:Ataxia Telangiectasia Mutated Proteins