{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T18:45:14Z","timestamp":1763837114742},"reference-count":75,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T00:00:00Z","timestamp":1397779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Although expressed in several haematological lineages and involved in multiple different signalling pathways, Bruton tyrosine kinase (<jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>) plays an indispensible role in B cells in signalling from the B cell receptor (<jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content>) for antigen. Many B cell malignancies remain dependent on constitutive <jats:styled-content style=\"fixed-case\">BCR<\/jats:styled-content> signalling, making <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> a functional therapeutic target. Several <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content> inhibitors (<jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>i) with different kinomes and modes of action are being assessed clinically. This review documents the efficacy and toxicity of <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>i in chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>). Clinically, the furthest in development is ibrutinib (trade name, Imbruvica), an irreversible <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>i, which has shown spectacular preliminary efficacy, with rapid reductions in lymph nodes accompanied by peripheral blood lymphocytosis. The lymphocytosis resolves slowly and most patients do not enter a complete remission. Nevertheless, it is possible to maintain many <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients, even those with adverse cytogenetic features, on drug for many months with minimal toxicities, thus potentially transforming the therapeutic paradigms for <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>. The efficacy, lack of toxicity and oral administration of <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>i will ensure their adoption in a wide range of B cell malignancies. An outstanding challenge is to incorporate <jats:styled-content style=\"fixed-case\">BTK<\/jats:styled-content>i with other precision medicines in a mechanism\u2010based manner in order to dispense with conventional chemotherapy.<\/jats:p>","DOI":"10.1111\/bjh.12895","type":"journal-article","created":{"date-parts":[[2014,4,19]],"date-time":"2014-04-19T10:10:46Z","timestamp":1397902246000},"page":"12-22","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Breaking good: the inexorable rise of <scp>BTK<\/scp> inhibitors in the treatment of chronic lymphocytic leukaemia"],"prefix":"10.1111","volume":"166","author":[{"given":"Claire V.","family":"Hutchinson","sequence":"first","affiliation":[{"name":"Department of of Cancer Studies and Molecular Medicine University of Leicester Leicester UK"},{"name":"The Ernest and Helen Scott Haematological Research Institute University of Leicester"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J. 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