The loss of Cbl E3 function can result in malignant transformation both in murine models and in human cancers due to hyperactivity of tyrosine kinases driven pathways [5, 6] There are three mammalian Cbl proteins: Cbl (a. k. a., c-Cbl, Cbl2, and RNF55), Cbl-b (a. k. a., RNF56), and Cbl-c (a.k.a., Cbl-3, Cbl-SL, and RNF57) [7]. This evidence concerns the gene CBL and cancer.