In CLL cells, the absence of the association of c-Cbl to CIN85 and Lyn, also after BCR triggering, together with the constitutive phosphorylation at Y731 and association to Cortactin in those patients in which Cortactin is highly expressed, sustain the hypothesis that c-Cbl has an altered protein structure that influences its activity and in turn cell homeostasis. This evidence concerns the gene SH3KBP1 and B-cell chronic lymphocytic leukemia.