@article{Ingrid M. Ariës_Bo R. Hansen_Troels Koch_Rosanna van den Dungen_William E. Evans_Rob Pieters_Monique L. den Boer_2013, place={Pavia, Italy}, title={The synergism of MCL1 and glycolysis on pediatric acute lymphoblastic leukemia cell survival and prednisolone resistance}, volume={98}, url={https://haematologica.org/article/view/6866}, DOI={10.3324/haematol.2013.093823}, abstractNote={<em>In vitro</em> and <em>in vivo</em> resistance to prednisolone are predictive for an adverse prognosis in pediatric precursor B-acute lymphoblastic leukemia. Causes of resistance are still poorly understood. In this study, we observed that prednisolone exposure of prednisolone-sensitive patients’ leukemic cells decreased anti-apoptotic MCL1 protein levels by 2.9-fold, while MCL1 protein expression in prednisolone-resistant leukemic patients’ cells was unaffected (<em>P</em><0.01). Locked nucleic acid oligonucleotides directed against MCL1 reduced MCL1 protein levels by 82±16% (<em>P</em><0.05) in leukemic cells, decreased proliferation by 9-fold and sensitized to prednisolone up to 80.8-fold, compared to a non-silencing-control locked nucleic acid (<em>P</em><0.05). Remarkably, we discovered that MCL1-silencing up-regulated the glucose consumption of leukemic cells by 2.5-fold (<em>P</em><0.05), suggesting a potential rescue mechanism mediated by glycolysis. Targeting glycolysis by 2-deoxyglucose synergistically inhibited leukemic survival by 23.2-fold in MCL1-silenced cells (<em>P</em><0.05). Moreover, 2-deoxyglucose and MCL1 locked nucleic acid concomitantly sensitized leukemic cells to prednisolone compared to MCL1 locked nucleic acid or 2-deoxyglucose alone (<em>P</em>&lt;0.05). In conclusion, these results indicate the need to target both MCL1 and glycolysis simultaneously to inhibit leukemic survival and sensitize acute leukemia patients towards prednisolone.}, number={12}, journal={Haematologica}, author={Ingrid M. Ariës and Bo R. Hansen and Troels Koch and Rosanna van den Dungen and William E. Evans and Rob Pieters and Monique L. den Boer}, year={2013}, month={Dec.}, pages={1905-1911} }