{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:41:18Z","timestamp":1793209278418,"version":"4.5.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,4,9]],"date-time":"2015-04-09T00:00:00Z","timestamp":1428537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["TRP6364-13"],"award-info":[{"award-number":["TRP6364-13"]}],"id":[{"id":"10.13039\/100005189","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":[[2015,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Bruton tyrosine kinase (<jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>), a mediator of B\u2010cell receptor (<jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>) signalling, has been implicated in the pathogenesis of chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>) and other B\u2010cell malignancies. Ibrutinib is an orally bioavailable and highly specific <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> inhibitor that was recently approved for treatment of patients with recurrent <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> and mantle cell lymphoma (<jats:styled-content style=\"fixed-case\">MCL<\/jats:styled-content>). In addition, ibrutinib has shown efficacy in subsets of patients with diffuse large B cell lymphoma (<jats:styled-content style=\"fixed-case\">DLBCL<\/jats:styled-content>) and Waldenstrom macroglobulinaemia (<jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content>). However, despite ibrutinib's activity in multiple B\u2010cell malignancies, cases of primary and secondary resistance have emerged. The overall reported frequency of resistance is low, but follow\u2010up in many trials was short, and we predict that the incidence of observed resistance will increase as clinical use outside clinical trials expands over time. Mutations within <jats:italic><jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content><\/jats:italic> have been described and clearly interfere with drug binding; however, there are also emerging alternative mechanisms that bypass <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> entirely and offer new opportunities for other targeted agents. Improved understanding of mechanisms of primary and secondary resistance is essential to developing appropriate therapeutic strategies to both prevent and address resistance. This review provides a comprehensive analysis of ibrutinib resistance in <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> MCL<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> DLBCL<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">WM<\/jats:styled-content> and considers potential strategies for further study.<\/jats:p>","DOI":"10.1111\/bjh.13427","type":"journal-article","created":{"date-parts":[[2015,4,10]],"date-time":"2015-04-10T03:59:00Z","timestamp":1428638340000},"page":"445-456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["Mechanisms of ibrutinib resistance in chronic lymphocytic leukaemia and non\u2010Hodgkin lymphoma"],"prefix":"10.1111","volume":"170","author":[{"given":"Shuang Q.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine Section of Haematology and Oncology 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