BCR and B-cell chronic lymphocytic leukemia: Since CLL cells depend on multiple survival and immune evasion strategies, we speculate that CLL cells in this model may eventually develop resistance mechanisms that allow disease progression, such as (1) clonal evolution of CLL B cells to depend on survival signaling unaffected by HDAC6 (2) mutation in BCR signaling kinases or (3) compensatory mechanisms through HDAC family members or epigenetic modulators with overlapping function.