Signaling Networks Associated with BCR–ABL–Dependent Transformation

BACKGROUND: The fusion protein BCR-ABL results in constitutive tyrosine kinase activity. It also affects downstream targets as well as the subcellular location of the normally tightly regulated Abl tyrosine kinase. METHODS: The authors review the current knowledge concerning the signaling networks associated with BCR-ABL-dependent transformation. RESULTS: Although BCR-ABL is considered a single genetic change, the dysregulated tyrosine kinase activates a network of signals that contributes to cytokine-independent growth, resistance to apoptosis, and genetic instability. CONCLUSIONS: The effectiveness of BCR-ABL-dependent transformation of hematopoietic stem cells is due not to a single pathway but rather to the culmination of a network of signaling pathways.