Considering that essentially all leukemia-associated Cbl mutants possess an intact TKB and C-terminal motifs that mediate interactions with a variety of signaling proteins, it is logical to hypothesize that these E3-defective proteins will be recruited to activated PTKs (via the TKB domain) and that this will lead to the formation of a signaling complex that lacks the negative regulatory function of wild-type Cbl. Here, CBL is linked to leukemia.