CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib‐resistant chronic myeloid leukaemia

A tyrosine kinase network composed of the TAM receptor AXL and the cytoplasmic kinases LYN and SYK is involved in nilotinib‐resistance of chronic myeloid leukaemia ( CML ) cells. Here, we show that the E3 ‐ubiquitin ligase CBL down‐regulation occurring during prolonged drug treatment plays a critical role in this process. Depletion of CBL in K562 cells increases AXL and LYN protein levels, promoting cell resistance to nilotinib. Conversely,...