Akt is activated in chronic lymphocytic leukemia cells Slides: 7 Download presentation Akt is activated in chronic lymphocytic leukemia cells and delivers a pro-survival signal: therapeutic potential of Akt inhibition by Jianguo Zhuang, Stephen F. Hawkins, Mark A. Glenn, Ke Lin, Gillian G. Johnson, Anthony Carter, John C. Cawley, and Andrew R. Pettitt haematol Volume 95(1): 110 -118 January 11, 2010 © 2010 by Ferrata Storti Foundation CLL cells express fully activated Akt. Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation Inhibition of Akt induces apoptosis in CLL cells. Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation Loss of MCL 1 through proteasomal degradation is involved in the apoptosis induced by Akt inhibition. Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation The pro-apoptotic effect of Akt inhibition involves both the GSK-3/MCL 1 and p 53 pathways. Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation The pro-apoptotic effect of Akt inhibitors is less potent in normal PBMC. (A) p-Akt is readily demonstrable in normal PBMC by western blotting (methods described in Figure 1). Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation Sensitivity of CLL cells to Akt inhibition correlates inversely with p 53 dysfunction and loss of 17 p/11 q, but not with other prognostic indicators. Jianguo Zhuang et al. Haematologica 2010; 95: 110 -118 © 2010 by Ferrata Storti Foundation Lymphocytic pleocytosisChronic myeloid leukemiaMark juckett mdCml stagesChronic myeloid leukemiaPromyelocyticNk leukemiaLll leukemia