Modeling the role of AKT in RT. (A) CLLs with high-risk features show constitutive activation of AKT (pAKT). (B) More than one-half of RTs show constitutive activation of AKT. (C) Genetic constitutive activation of AKT in the TCL1 mouse model leads to expansion of microenvironment CD4 cells expressing the NOTCH ligand DLL1, leading to activation of NOTCH1, which drives transformation.