It is tempting to speculate that CD137 induction may contribute to the development or progression of CLL in this microenvironment through two mechanisms: (i) the intrinsic induction of survival factor(s) by NF-κB activation by CD137 signaling and (ii) the inhibition of T-cell co-stimulation through CD137 by competitive binding with CD137L (Fig. 6). This evidence concerns the gene TNFRSF9 and B-cell chronic lymphocytic leukemia.