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Intrinsic apoptosis is the cell's self-destruct switch. BCL-2 holds it shut; BAX and BAK pull it open. Venetoclax pries BCL-2 off so the switch can fire.
Stress signals induce BH3-only proteins (BIM, PUMA, NOXA, BAD) that either inhibit anti-apoptotic BCL-2, BCL-XL, MCL-1 or directly activate BAX/BAK, which permeabilise the mitochondrial outer membrane, releasing cytochrome c to activate caspase-9 and executioner caspases. Cancers overexpress BCL-2 (t(14;18) in follicular lymphoma; CLL), MCL-1 (myeloma, AML), or BCL-XL (solid tumours, platelets). Venetoclax (BCL-2) transformed CLL and AML; MCL-1 inhibitors have cardiac toxicity; BCL-XL degraders and platelet-sparing PROTACs are in development.
A dam (mitochondrial membrane) held by guards (BCL-2, MCL-1) against demolition crews (BAX/BAK). Cancer hires extra guards. Venetoclax fires the BCL-2 guards, and the dam breaks.
Shares Double expressor: MYC and BCL2 protein together by immunohistochemistry, Double-hit / high-grade B-cell lymphoma, MicroRNAs in cancer, Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement.
Shares VIALE-A, Sonrotoclax, Acute myeloid leukaemia in older or unfit patients, Chronic lymphocytic leukaemia, first treatment.
Shares BCL2 rearrangement, t(14;18), The germinal centre reaction, The germinal centre: why lymphoma starts where antibodies are made, BCL-2.
Shares Venetoclax + hypomethylating agent, VIALE-A, Acute myeloid leukaemia in older or unfit patients, BCL-2.
Shares BAX, BIM (BCL2L11), BH3 profiling (functional apoptosis testing), VIALE-A.
Shares Double-hit / high-grade B-cell lymphoma, Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement, The germinal centre reaction, The germinal centre: why lymphoma starts where antibodies are made.
Shares Relapsed or refractory chronic lymphocytic leukaemia, Venetoclax, Myelodysplastic syndromes / neoplasms (MDS), TP53.
Shares Double expressor: MYC and BCL2 protein together by immunohistochemistry, The germinal centre reaction, The germinal centre: why lymphoma starts where antibodies are made, BCL-2.