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Recent evidence shows that TE reactivation induces innate immune signaling, DNA damage responses, and dependence on poly(ADP-ribose) polymerase (PARP)\u2013mediated protection, enabling synthetic lethality with PARP inhibition even in homologous recombination\u2013proficient leukemias with epigenetic gene mutations. In this article, we highlight the biology underpinning this novel TE-PARP axis, its therapeutic implications, and strategies to expand PARP inhibition beyond HR-deficient cancers through rational combinations with immunotherapy and refined patient stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2025032216","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T20:55:53Z","timestamp":1773262553000},"page":"2035-2040","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["The transposable element\u2013PARP axis underpins synthetic lethality and immunogenic vulnerability in blood cancer"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-6367","authenticated-orcid":false,"given":"Bernd B.","family":"Zeisig","sequence":"first","affiliation":[{"name":"1Comprehensive Cancer Centre, King\u2019s College London, London, United 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