Resistance to B-cell receptor inhibitors is independent of AID-induced genome instability in Chronic Lymphocytic Leukemia
Overall, our study demonstrates that CLL patients accumulate mutations in genes recognized as AID off-targets after treatment with idelalisib and ibrutinib. Furthermore, we were able to recapitulate this characteristicmutational activity in experimental models of AID WT or KO CLL lines, mechanistically corroborating the findings in patients. However, although APOBEC family-mediated mutagenesis has been linked to drug resistance in other cancers, our findings suggest that AID-driven mutations are not a primary mechanism of BCR inhibitor resistance in CLL.