{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:12:40Z","timestamp":1771038760524,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,5]],"date-time":"2025-10-05T00:00:00Z","timestamp":1759622400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    BCL2 inhibitors (BCL2i) have transformed the management of chronic lymphocytic leukaemia (CLL), but their use in more aggressive B\u2010cell malignancies such as diffuse large B\u2010Cell lymphoma (DLBCL) is complicated by the more heterogeneous nature of the disease. Successful responses are limited to a subset of patients, highlighting the need for robust biomarkers predicting sensitivity. Here, we investigated the underlying mechanisms of inherent resistance to the BCL2i ABT\u2010199 and BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    inhibitor A1331852, focusing on the roles of the principal pro\u2010apoptotic BH3\u2010only proteins NOXA and BIM. We show that NOXA deletion, but not BIM deletion, in BCL2 and BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    \u2010dependent DLBCL cells both in\u00a0vitro and in\u00a0vivo resulted in a highly significant enhanced resistance to both BCL2i and BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    inhibitors. In contrast, NOXA deletion did not result in alteration of sensitivity to MCL1 inhibitors. NOXA loss was associated with increased stability and binding capacity of MCL1; binding of BIM to MCL1 was associated with resistance to ABT\u2010199. Resistance to BCL2i and BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    inhibitors was abrogated by suppression of MCL1 expression. In conclusion, we show that NOXA is essential for the effectiveness of BH3\u2010mimetics targeting BCL2\/BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    ; in the absence of NOXA, BIM displaced from BCL2\/BCL\u2010X\n                    <jats:sub>L<\/jats:sub>\n                    can be bound by MCL1.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70192","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T04:47:57Z","timestamp":1759726077000},"page":"96-105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>BH3<\/scp>\n                    \u2010only protein\n                    <scp>NOXA<\/scp>\n                    is essential for apoptosis induction by\n                    <scp>BH3<\/scp>\n                    \u2010mimetics targeting\n                    <scp>BCL2<\/scp>\n                    or\n                    <scp>BCL<\/scp>\n                    \u2010\n                    <scp>\n                      X\n                      <sub>L<\/sub>\n                    <\/scp>\n                    in\n                    <scp>DLBCL<\/scp>"],"prefix":"10.1111","volume":"208","author":[{"given":"Nahide","family":"Yildirim","sequence":"first","affiliation":[{"name":"Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius","family":"Anders","sequence":"additional","affiliation":[{"name":"Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria M.","family":"Smith","sequence":"additional","affiliation":[{"name":"The Ernest and Helen Scott Haematological Research Institute Leicester Cancer Research Centre, University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Jayne","sequence":"additional","affiliation":[{"name":"The Ernest and Helen Scott Haematological Research Institute Leicester Cancer Research Centre, University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Assmann","sequence":"additional","affiliation":[{"name":"Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekah","family":"Jukes\u2010Jones","sequence":"additional","affiliation":[{"name":"The Ernest and Helen Scott Haematological Research Institute Leicester Cancer Research Centre, University of Leicester  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-2236","authenticated-orcid":false,"given":"Martin J. 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