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.