We have recently shown that the p66Shc expression defect in CLL cells leads to a decrease in the intracellular ROS levels, which in turn abnormally enhance the transcriptional activity of the ROS-sensitive p65 subunit of NF-κB (Tatangelo et al., 2022) and promotes IL-9 release by CLL cells (Patrussi et al., 2021a), thereby contributing to shape the tumor niche to a pro-survival one (Patrussi et al., 2021a; Patrussi et al., 2021b). The gene discussed is IL9; the disease is B-cell chronic lymphocytic leukemia.