Proposed model of the p66Shc-mediated IL-9 crosstalk between CLL and stroma cells. Low levels of p66Shc in CLL cells simultaneously enhance the expression of homing receptors and permit the transcription of IL-9 in an ROS-dependent manner. CLL-derived and secreted IL-9 binds to IL-9-receptors expressed on stroma cells and drives the expression of homing cytokines, further attracting CLL cells to their niche. Created with BioRender.com.