{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:17:30Z","timestamp":1789010250156,"version":"build-2803163510"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Targeting the B-cell receptor signaling pathway through BTK inhibition proved to be effective for the treatment of chronic lymphocytic leukemia (CLL) and other B-cell lymphomas. Covalent BTK inhibitors (BTKis) led to an unprecedented improvement in outcome in CLL, in particular for high-risk subgroups with\n                    <jats:italic>TP53<\/jats:italic>\n                    aberration and unmutated immunoglobulin heavy-chain variable-region gene (IGHV). Ibrutinib and acalabrutinib are approved by the US Food and Drug Administration for the treatment of CLL and other B-cell lymphomas, and zanubrutinib, for patients with mantle cell lymphoma. Distinct target selectivity of individual BTKis confer differences in target-mediated as well as off-target adverse effects. Disease progression on covalent BTKis, driven by histologic transformation or selective expansion of\n                    <jats:italic>BTK<\/jats:italic>\n                    and\n                    <jats:italic>PLCG2<\/jats:italic>\n                    mutated CLL clones, remains a major challenge in the field. Fixed duration combination regimens and reversible BTKis with non-covalent binding chemistry hold promise for the prevention and treatment of BTKi-resistant disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.687458","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T03:23:03Z","timestamp":1624418583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":77,"title":["Targeting Bruton\u2019s Tyrosine Kinase in CLL"],"prefix":"10.3389","volume":"12","author":[{"given":"Inhye E.","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer 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