{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T17:13:38Z","timestamp":1791825218728,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIGMS\/NIH","award":["R35GM151109"],"award-info":[{"award-number":["R35GM151109"]}]},{"name":"NIGMS\/NIH","award":["K08CA230319"],"award-info":[{"award-number":["K08CA230319"]}]},{"name":"NCI\/NIH","award":["R35GM151109"],"award-info":[{"award-number":["R35GM151109"]}]},{"name":"NCI\/NIH","award":["K08CA230319"],"award-info":[{"award-number":["K08CA230319"]}]},{"name":"Doris Duke Charitable Foundation","award":["R35GM151109"],"award-info":[{"award-number":["R35GM151109"]}]},{"name":"Doris Duke Charitable Foundation","award":["K08CA230319"],"award-info":[{"award-number":["K08CA230319"]}]},{"name":"Edward P. Evans Foundation","award":["R35GM151109"],"award-info":[{"award-number":["R35GM151109"]}]},{"name":"Edward P. Evans Foundation","award":["K08CA230319"],"award-info":[{"award-number":["K08CA230319"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bruton\u2019s tyrosine kinase (BTK), a non-receptor tyrosine kinase crucial for B cell development and function, acts downstream of the B cell receptor (BCR) in the BCR pathway. Other kinases involved downstream of the BCR besides BTK such as Syk, Lyn, PI3K, and Mitogen-activated protein (MAP) kinases also play roles in relaying signals from the BCR to provide pro-survival, activation, and proliferation cues. BTK signaling is implicated in various B-cell lymphomas such as mantle cell lymphoma, Waldenstr\u00f6m Macroglobulinemia, follicular lymphoma, and diffuse large B cell lymphoma, leading to the development of transformative treatments like ibrutinib, the first-in-class covalent BTK inhibitor, and pirtobrutinib, the first-in-class noncovalent BTK inhibitor. However, kinase-deficient mutations C481F, C481Y, C481R, and L528W in the BTK gene confer resistance to both covalent and non-covalent BTK inhibitors, facilitating B cell survival and lymphomagenesis despite kinase inactivation. Further studies have revealed BTK\u2019s non-catalytic scaffolding function, mediating the assembly and activation of proteins including Toll-like receptor 9 (TLR9), vascular cell adhesion protein 1 (VCAM-1), hematopoietic cell kinase (HCK), and integrin-linked kinase (ILK). This non-enzymatic role promotes cell survival and proliferation independently of kinase activity. Understanding BTK\u2019s dual roles unveils opportunities for therapeutics targeting its scaffolding function, promising advancements in disrupting lymphomagenesis and refining B cell lymphoma treatments.<\/jats:p>","DOI":"10.3390\/ijms25147516","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T08:38:04Z","timestamp":1720514284000},"page":"7516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Evolving Role of Bruton\u2019s Tyrosine Kinase Inhibitors in B Cell Lymphomas"],"prefix":"10.3390","volume":"25","author":[{"given":"Shefali","family":"Mehra","sequence":"first","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8747-1432","authenticated-orcid":false,"given":"Miah","family":"Nicholls","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, University of Miami, Coral Gables, FL 33146, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4407-6325","authenticated-orcid":false,"given":"Justin","family":"Taylor","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12943-018-0779-z","article-title":"Role of Bruton\u2019s tyrosine kinase in B cells and malignancies","volume":"17","author":"Dammeijer","year":"2018","journal-title":"Mol. 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