Figure 2.

 Residual CML stem cells are responsible for TKI resistance in CML patients. CML arises in HSCs due to activity of the oncogenic BCR–ABL fusion protein. The TKI imatinib, which inhibits ABL tyrosine kinase activity, is now standard therapy for CML. Imatinib can eradicate numerous CML cells, such as progenitor‐like CML cells and differentiated CML cells, and significantly improves the prognosis of CML patients in the chronic phase. However, it does not deplete CML stem cells, which top the CML hierarchy and are responsible for disease recurrence. Thus, effective human CML therapy requires measures to eradicate TKI‐resistant CML stem cells. Ph⁺, Philadelphia chromosome‐positive CML cells.