Towards a Cure for CML by Targeting Dormant Leukaemic Stem Cells

Tyrosine kinase inhibitors (TKIs) have transformed the lives of patients with chronic myeloid leukaemia (CML). ~25% will be able to stop therapy and maintain remission – termed treatmentfree remission (TFR). We hypothesise that failure to achieve TFR in the remaining 75% relates to persistence of a population of “dormant” leukaemic stem cells that are rendered insensitive to TKI therapy. Cancer stem cell dormancy is a recognised cause of relapse in many cancers. These cells reside in a specialised niche in the bone marrow where they evade targeted therapy because they remain in a dormant state.

One promising approach to maximising TFR is to “awaken” the dormant cells, rendering them sensitive to TKI therapy as they divide and exit the bone marrow. We will identify and characterise these dormant cells, then use novel drugs to activate and sensitise them to TKI-mediated eradication. This represents a new pathway to cure in CML.