Integrin signaling in CLL. (A) Inside-out integrin signaling. Signaling through the BCR, dependent on Btk and PLC-γ2, activates the cytoplasmic domain of the integrin, causing a conformational change to the open, active form. This form has high affinity for ligand binding and induces cell migration and adhesion. (B) Outside-in integrin signaling. Ligand binding to an integrin induces signals that can lead to growth, differentiation, survival, or apoptosis.