Figure 2.

CML pathogenesis and treatment. (A) Normal (blue) and leukaemic (grey) stem cells are regularly activated from their bone marrow niches (bottom, signalling context A) and subsequently divide (signalling context Ω). For the maintenance of a balance between quiescent and activated cells, some cells return to the niches and self-renew while others undergo further proliferation and differentiation, and contribute to peripheral blood. Owing to an increased activation of the leukaemic cells compared with normal cells the leukaemic pool slowly outcompetes normal haematopoiesis. (B) TKIs preferentially target activated leukaemic cells, thus leading to a significant reduction of tumour load. However, we also assume that leukaemic stem cells are even less likely to be activated under TKI treatment (indicated by the thinner arrows). Therefore, a residual pool of leukaemic cells persists over long time scales. (C) IFNα-mediated activation of both normal and leukaemic stem cells leads to a fast and sustained reduction of the residual leukaemic cells as these activated leukaemic (stem) cells are target for the primary TKI-mediated cell kill.