Considering that several microenvironment stimuli of CLL cells, including growth factors, cytokines, integrins and BCR, promote the activation of AKT and other kinases, that in turn inactivate GSK3β by S9 phosphorylation, GSK3β inactivation may represent a crucial event on which multiple extracellular signals converge for sustaining NOTCH1 signaling. Here, NOTCH1 is linked to B-cell chronic lymphocytic leukemia.