Unlike CML, CLL cells do not have any selective genetic lesion that is associated with the pathophysiology of the disease. On the contrary, B-cell receptor–mediated signaling and interactions with the microenvironment have been shown to maintain CLL lymphocytes. Unlike a single kinase, Bcr-Abl in CML, CLL offers several kinases to target, and selective small-molecule kinase inhibitors are recognized and tested. PI3K indicates phosphatidylinositol 3-kinase; SYK, spleen tyrosine kinase; and BTK, Bruton tyrosine kinase. Professional illustration by Marie Dauenheimer.