Hedgehog/GLI and PI3K signaling in the initiation and maintenance of chronic lymphocytic leukemia
D Kern, G Regl, SW Hofbauer, P Altenhofer, G Achatz, A Dlugosz, H Schnidar, R Greil, TN Hartmann and F Aberger
Abstract:
The study addressed the role of Hedgehog (HH)/GLI and its putative interaction with the PI3K/AKT cascade in the initiation and maintenance of chronic lymphocytic leukemia (CLL). Using transgenic mouse models, we show that HH/GLI signaling alone or in combination with PI3K/AKT does not suffice to initiate a CLL-like phenotype. By contrast, our work identifies a critical role of GLI and PI3K signaling for the survival of human primary CLL cells, and further shows that combined targeting of GLI and PI3K/AKT/mTOR signaling has a synergistic therapeutic effect. The data provide a basis for rational combination therapies targeting HH/GLI and PI3K signaling in this common hematopoietic malignancy.    

The open access article can be found  here.  

Reviewed by Hans Brandstetter