Constitutive IP3 signaling is therefore an additional determinant of the sensitivity of B-cell cancers, like DLBCL and CLL, to BIRD-2, a Bcl-2 inhibitor that targets its BH4 domain and alleviates Bcl-2′s inhibitory role on IP3R channels. This evidence concerns the gene ITPR3 and B-cell chronic lymphocytic leukemia.