Mechanism of VEN resistance. (1) The proapoptotic BH3-only protein binds to antiapoptotic protein BCL2. (2) VEN is a BH3 mimetic that binds to BCL2, which leads to displacement of BH3-only protein. (3) In the setting of VEN resistance, increased levels of antiapoptotic proteins such as MCL-1, BCLX_L, and BCL2A1 sequester BH3-only proteins. (4) Consequently, there are fewer BH3-only proteins available to induce apoptosis. Created with BioRender.com.