@article{Angelo Agathanggelou_Victoria J. Weston_Tracey Perry_Nicholas J. Davies_Anna Skowronska_Daniel T. Payne_John S. Fossey_Ceri E. Oldreive_Wenbin Wei_Guy Pratt_Helen Parry_David Oscier_Steve J. Coles_Paul S. Hole_Richard L. Darley_Michael McMahon_John D. Hayes_Paul Moss_Grant S. Stewart_A. Malcolm R. Taylor_Tatjana Stankovic_2015, place={Pavia, Italy}, title={Targeting the Ataxia Telangiectasia Mutated-null phenotype in chronic lymphocytic leukemia with pro-oxidants}, volume={100}, url={https://haematologica.org/article/view/7465}, DOI={10.3324/haematol.2014.115170}, abstractNote={Inactivation of the Ataxia Telangiectasia Mutated gene in chronic lymphocytic leukemia results in resistance to p53-dependent apoptosis and inferior responses to treatment with DNA damaging agents. Hence, p53-independent strategies are required to target Ataxia Telangiectasia Mutated-deficient chronic lymphocytic leukemia. As Ataxia Telangiectasia Mutated has been implicated in redox homeostasis, we investigated the effect of the Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia genotype on cellular responses to oxidative stress with a view to therapeutic targeting. We found that in comparison to Ataxia Telangiectasia Mutated-wild type chronic lymphocytic leukemia, pro-oxidant treatment of Ataxia Telangiectasia Mutated-null cells led to reduced binding of NF-E2 p45-related factor-2 to antioxidant response elements and thus decreased expression of target genes. Furthermore, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia cells contained lower levels of antioxidants and elevated mitochondrial reactive oxygen species. Consequently, Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia, but not tumors with 11q deletion or <em>TP53</em> mutations, exhibited differentially increased sensitivity to pro-oxidants both <em>in vitro</em> and <em>in vivo</em&gt;. We found that cell death was mediated by a p53- and caspase-independent mechanism associated with apoptosis inducing factor activity. Together, these data suggest that defective redox-homeostasis represents an attractive therapeutic target for Ataxia Telangiectasia Mutated-null chronic lymphocytic leukemia.}, number={8}, journal={Haematologica}, author={Angelo Agathanggelou and Victoria J. Weston and Tracey Perry and Nicholas J. Davies and Anna Skowronska and Daniel T. Payne and John S. Fossey and Ceri E. Oldreive and Wenbin Wei and Guy Pratt and Helen Parry and David Oscier and Steve J. Coles and Paul S. Hole and Richard L. Darley and Michael McMahon and John D. Hayes and Paul Moss and Grant S. Stewart and A. Malcolm R. Taylor and Tatjana Stankovic}, year={2015}, month={Aug.}, pages={1076-1085} }