{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T03:30:40Z","timestamp":1786505440332,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005416","name":"Norges Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["332640"],"award-info":[{"award-number":["332640"]}],"id":[{"id":"10.13039\/501100005416","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":[[2026,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Targeted therapies have transformed modern management of chronic lymphocytic leukaemia (CLL). Still, CLL remains an incurable disease, and key unresolved challenges include development of treatment resistance and intolerance. To address these challenges, it is necessary to define clinically actionable biomarkers that can predict individual treatment responses. Here, we aimed to map the treatment sensitivity and resistance landscapes of CLL cells from treatment\u2010na\u00efve and treatment\u2010exposed patients to understand the evolution of treatment vulnerabilities. We performed ex\u00a0vivo drug screens with 94 single agents and 87 drug combinations on CLL cells from treatment\u2010na\u00efve, ibrutinib\u2010exposed or idelalisib\u2010exposed patients. We found that overall drug sensitivity was reduced in cells from patients who had received treatment. Specifically, sensitivity to B\u2010cell lymphoma 2 (Bcl\u20102) inhibitors was significantly reduced in both ibrutinib\u2010exposed and idelalisib\u2010exposed patient cells. Furthermore, combined Bruton's tyrosine kinase inhibitor (BTK)\/Bcl\u20102 inhibition became less relevant in advanced disease, while dual mitogen\u2010activated protein kinase kinase (MEK)\/Bcl\u20102 inhibition was identified as an effective new treatment modality. Our findings provide valuable insights that may assist clinical decisions regarding treatment sequencing and treatment options for relapsed\/refractory disease.<\/jats:p>","DOI":"10.1111\/bjh.70603","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:30:15Z","timestamp":1781094615000},"page":"469-479","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evolution of the drug sensitivity landscape of chronic lymphocytic leukaemia"],"prefix":"10.1111","volume":"209","author":[{"given":"Johanne U.","family":"Hermansen","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology, Institute for Cancer Research Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Institute for Cancer Research Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7757-4091","authenticated-orcid":false,"given":"Geir E.","family":"Tj\u00f8nnfjord","sequence":"additional","affiliation":[{"name":"Department of Haematology Oslo University Hospital  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Mato","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-356X","authenticated-orcid":false,"given":"Sigrid S.","family":"Sk\u00e5nland","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Institute for Cancer Research Oslo University Hospital  Oslo 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