In this study, we have shown that overexpression of SIRT3 and variable degrees of promoter methylation of the catalase gene may impair ROS clearance leading to accumulation of H2O2 in CLL cells which, on the other hand, activates the AXL/AKT/ERK and fibroblast growth factor receptor (FGFR) cell survival signaling axes. Here, CAT is linked to B-cell chronic lymphocytic leukemia.