BCL6 enables Ph+ acute lymphoblastic leukaemia cells to survive BCR–ABL1 kinase inhibition

Targeted cancer therapies are often associated with drug resistance, a phenomenon that has been observed with tyrosine kinase inhibitors (TKIs), widely used to treat leukaemia driven by BCR–ABL1 mutations. Markus Mueschen and colleagues describe a novel BCL6-dependent mechanism of drug resistance in leukaemia through which TKI-induced upregulation of BCL6 allows leukemia cells to cope with acute oncogene withdrawal. Targeted inhibition of BCL6 reduces the number of drug-resistant and self-renewing leukaemia-initiating cells. In xenograft models of acute lymphoblastic leukaemia cells carrying BCR–ABL1 mutations, dual inhibition of BCR–ABL1 and BCL6 prevents resistance and improves the anticancer response.