[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Neoplasia](https://durgical.com/en/general-pathology/#a-neoplasia) › Evading cell death and replicating without limit: BCL2 and telomerase [General pathology](https://durgical.com/en/general-pathology/) · [Neoplasia](https://durgical.com/en/general-pathology/#a-neoplasia) # Evading cell death and replicating without limit: BCL2 and telomerase - Mechanism Cancer cells switch off their own self-destruct programme and rebuild the ends of their chromosomes so they can divide forever. Updated 2026-11-01 ## Key points - Intrinsic pathway: BCL2 and BCL-XL guard the mitochondrion; BAX and BAK open it; cytochrome c release activates caspase 9 and then caspase 3. - t(14;18) puts BCL2 under the immunoglobulin heavy chain promoter: follicular lymphoma grows by failing to die, not by dividing fast. - In chronic lymphocytic leukaemia BCL2 is overexpressed; BCL2 inhibitors (BH3 mimetics) exploit this. - Loss of p53 removes the signal that sends damaged cells to apoptosis. - Telomeres shorten with each division; telomerase (TERT) is reactivated in most cancers; some use alternative lengthening instead. - Defective telomerase in the germline causes dyskeratosis congenita (marrow failure), the opposite problem. ## What it is Normal cells with damaged DNA or lost signals die by apoptosis, and normal cells can divide only a limited number of times before short telomeres stop them. Cancer cells escape both limits: they disable the intrinsic (mitochondrial) apoptotic pathway, often by overexpressing BCL2 or losing p53, and they reactivate telomerase to maintain telomeres. Together these traits let a clone survive long enough to accumulate the rest of its mutations. ## Function - Escape from apoptosis gives time for further mutations and explains resistance to chemotherapy and radiation, which kill largely by triggering apoptosis. - Loss of p53 and RB also lets cells bypass senescence, the permanent growth arrest of ageing cells. - Telomere crisis before telomerase reactivation may cause chromosome fusions, a source of genomic instability. ## Step by step - DNA damage or growth factor withdrawal activates BH3-only sensor proteins. - Sensors neutralise BCL2 and BCL-XL and free BAX and BAK. - BAX and BAK form pores in the outer mitochondrial membrane; cytochrome c leaks out. - Cytochrome c joins APAF1 in the apoptosome, which activates caspase 9 and then caspase 3. - In cancer, extra BCL2 or absent p53 blocks this chain, so damaged cells survive. - Each division shortens telomeres; very short telomeres normally trigger senescence or crisis. - Cancer cells that switch on TERT keep their telomeres long and escape this limit. ## Clinical notes - Follicular lymphoma is usually indolent but hard to cure because its cells resist death. - BCL2 inhibitors are used in chronic lymphocytic leukaemia and some acute myeloid leukaemias; rapid killing can cause tumour lysis syndrome. - TERT promoter mutations are frequent in melanoma, glioblastoma and bladder cancer. ## Memory aid BCL2 is the guard who hides the self-destruct button; telomerase is the mechanic who keeps resetting the cell's odometer to zero. ## Test yourself Think of the answer, then tap the question to see it. ## What translocation overexpresses BCL2 and in which tumour? t(14;18) between IGH and BCL2, characteristic of follicular lymphoma. ## Why does follicular lymphoma grow slowly but resist cure? Its cells accumulate because they fail to undergo apoptosis rather than because they divide fast. ## Which enzyme lets cancer cells keep dividing indefinitely? Telomerase (catalytic subunit TERT), which adds telomeric repeats to chromosome ends. ## Which molecule released from mitochondria triggers the apoptosome? Cytochrome c, which binds APAF1 and activates caspase 9. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/evading-cell-death-and-replicating-without-limit-bcl2-and-telomerase/) ## Related - [Apoptosis: the intrinsic and extrinsic pathways](https://durgical.com/en/general-pathology/apoptosis-the-intrinsic-and-extrinsic-pathways/) - [The hallmarks of cancer](https://durgical.com/en/general-pathology/the-hallmarks-of-cancer/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) - [Cellular aging: telomeres, DNA damage, senescence and proteostasis](https://durgical.com/en/general-pathology/cellular-aging-telomeres-dna-damage-senescence-and-proteostasis/) - [Translocations, amplifications and epigenetic changes in cancer](https://durgical.com/en/general-pathology/translocations-amplifications-and-epigenetic-changes-in-cancer/) - [The cell cycle in cancer: cyclins, CDKs and checkpoints](https://durgical.com/en/general-pathology/the-cell-cycle-in-cancer-cyclins-cdks-and-checkpoints/) ## Related conditions - [Non-Hodgkin lymphoma](https://durgical.com/en/conditions/non-hodgkin-lymphoma/) - [Chronic lymphocytic leukaemia](https://durgical.com/en/conditions/chronic-lymphocytic-leukaemia/) - [Dyskeratosis congenita and other telomere biology disorders](https://durgical.com/en/conditions/dyskeratosis-congenita-and-other-telomere-biology-disorders/) - [Lung cancer](https://durgical.com/en/conditions/lung-cancer/) - [Melanoma](https://durgical.com/en/conditions/melanoma/) ## Elsewhere in DurgiPedia - [Telomerase](https://durgical.com/en/biochemistry/enzymes/telomerase/) - [Cell injury, apoptosis and necrosis](https://durgical.com/en/histology/cell-injury-apoptosis-and-necrosis/) - [Cytochrome c](https://durgical.com/en/biochemistry/enzymes/cytochrome-c/) - [Cell cycle, mitosis and meiosis](https://durgical.com/en/histology/cell-cycle-mitosis-and-meiosis/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [TERT gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/tert/) (MedlinePlus, US National Library of Medicine, 2026); [TP53 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/tp53/) (MedlinePlus, US National Library of Medicine, 2026); [Targeted Therapy to Treat Cancer](https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies) (National Cancer Institute (NCI), 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/evading-cell-death-and-replicating-without-limit-bcl2-and-telomerase/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/evading-cell-death-and-replicating-without-limit-bcl2-and-telomerase/