CLL cells are exquisitely dependent on the B-cell lymphoma 2 (BCL-2) anti-apoptotic protein for survival99, and the “BH3-mimetic” navitoclax, an antagonist of both BCL-2 and BCL-xL, showed promising activity in patients with R/R CLL100, but the development of this agent was hampered by the occurrence of dose-limiting thrombocytopenia in all clinical trials, an on-target consequence of the drug’s action on platelets and megakaryocytes, which rely on BCL-xL for survival101. This evidence concerns the gene BCL2 and B-cell chronic lymphocytic leukemia.