Fig. 1. Roles of BCR-ABL kinase activity-independent Src pathway and leukaemic stem cells in ALL therapy.
Because the activation of Src kinases is independent of BCR-ABL kinase activity, inhibition of BCR-ABL kinase activity by imatinib does not reduce BCR-ABL-stimulated Src activation. Inhibition of Src kinases may have a cytostatic effect on ALL stem cells, but these cells also survive through other unknown mechanisms. Therefore, simultaneous inhibition of functions of both BCR-ABL (by imatinib) and Src kinases (by an Src kinase inhibitor) and leukaemic stem cells (by an anti-stem cell agent to be developed) is needed for curative therapy of Ph+ B-ALL. cc: coiled-coil domain; Y177: tyrosine 177; SH: Src homology domain.