Src kinases as targets for B cell acute lymphoblastic leukaemia therapy.

The participation of Src kinases in the induction of BCR-ABL-induced B cell acute lymphoblastic leukaemia (B-ALL), but not chronic myeloid leukaemia (CML), demonstrates cell type-specific signalling in Philadelphia chromosome-positive (Ph+) leukaemias. Different therapeutic strategies are therefore needed for B-ALL and CML. Activation of Src kinases is independent of BCR-ABL kinase activity for activation. Thus, Src kinases provide a mechanism for resistance to the BCR-ABL kinase inhibitors and potential targets for B-ALL therapy. Simultaneous targeting of both BCR-ABL and Src kinases may benefit human B-ALL patients. Leukaemic stem cells may exist in Ph+ B-ALL, and eradication of this group of cells would provide a curative method for this disease.