Several DNA damage response genes (i.e., ATM, TP53, CHEK1, CHEK2, ERCC4, BRCA1, FANCA, MSH4, SMC1A, RAD50, and MCM3) have previously been shown to be mutated frequently in CLL and to be associated with advanced tumor evolution, immune surveillance escape, and adverse patient outcomes and chemotherapy responses [8,9,10,11,12,13]. This evidence concerns the gene MSH4 and B-cell chronic lymphocytic leukemia.