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IFN-? wakes up sleeping hematopoietic stem cells- Emmanuelle Passegué & Patricia Ernst Nature Medicine

Persistent CML-initiating cells, or CML stem cells, which are protected from imatinib killing by their quiescent status, are probably responsible for the regrowth of the disease.



The emerging possibility to explain the stable remission in the patients previously treated with IFN-? could be that the exposure
to IFN-? induced the CML stem cells to exit quiescence and
proliferate such that, upon imatinib treatment, they became vulnerable to imatinib rather than remaining protected.


Although the results of the patient studies need to be confirmed in larger studies, they raise the tantalizing possibility of an effective targeting strategy for drug-resistant quiescent
cancer stem cells in individuals suffering from CML and other hematologic malignancies.


These new insights into the role of IFN signaling in normal HSC quiescence may spark further interest in manipulating this pathway to kick quiescent leukemia stem cells into a more vulnerable state.