Indeed, it has been shown in MCL and CLL, that a subgroup of cell lines resistant to classical BCR signaling and canonical pathway activation by drugs such as fludarabine and ibrutinib, respectively, exhibited non-canonical pathway activation and BIRC3 mutations (Rahal et al. 2014; Diop et al. 2020). Here, BIRC3 is linked to B-cell chronic lymphocytic leukemia.