{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:13:49Z","timestamp":1789964029959,"version":"4.0.1"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T00:00:00Z","timestamp":1409875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2015,4]]},"DOI":"10.1038\/leu.2014.263","type":"journal-article","created":{"date-parts":[[2014,9,5]],"date-time":"2014-09-05T06:37:24Z","timestamp":1409899044000},"page":"895-900","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["Functional characterization of BTKC481S mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors"],"prefix":"10.1038","volume":"29","author":[{"given":"S","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y L","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,9,5]]},"reference":[{"key":"BFleu2014263_CR1","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/nri3487","volume":"13","author":"RC Rickert","year":"2013","unstructured":"Rickert RC . New insights into pre-BCR and BCR signalling with relevance to B cell malignancies. Nat Rev Immunol 2013; 13: 578\u2013591.","journal-title":"Nat Rev Immunol"},{"key":"BFleu2014263_CR2","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.molimm.2004.04.008","volume":"41","author":"JM Dal Porto","year":"2004","unstructured":"Dal Porto JM, Gauld SB, Merrell KT, Mills D, Pugh-Bernard AE, Cambier J . B cell antigen receptor signaling 101. Mol Immunol 2004; 41: 599\u2013613.","journal-title":"Mol Immunol"},{"key":"BFleu2014263_CR3","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1146\/annurev.immunol.021908.132541","volume":"28","author":"T Kurosaki","year":"2009","unstructured":"Kurosaki T, Shinohara H, Baba Y . B cell signaling and fate decision. Annu Rev Immunol 2009; 28: 21\u201355.","journal-title":"Annu Rev Immunol"},{"key":"BFleu2014263_CR4","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1146\/annurev-immunol-030409-101216","volume":"28","author":"NE Harwood","year":"2010","unstructured":"Harwood NE, Batista FD . Early events in B cell activation. Annu Rev Immunol 2010; 28: 185\u2013210.","journal-title":"Annu Rev Immunol"},{"key":"BFleu2014263_CR5","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1200\/JCO.2012.42.7906","volume":"31","author":"RH Advani","year":"2013","unstructured":"Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed\/refractory B-cell malignancies. J Clin Oncol 2013; 31: 88\u201394.","journal-title":"J Clin Oncol"},{"key":"BFleu2014263_CR6","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1056\/NEJMoa1215637","volume":"369","author":"JC Byrd","year":"2013","unstructured":"Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med 2013; 369: 32\u201342.","journal-title":"N Engl J Med"},{"key":"BFleu2014263_CR7","first-page":"7014","volume":"31","author":"BY Chang","year":"2013","unstructured":"Chang BY, Furman RR, Zapatka M, Barrientos JC, Li D, Steggerda S et al. Use of tumor genomic profiling to reveal mechanisms of resistance to the BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL). ASCO Meet Abstr 2013; 31: 7014.","journal-title":"ASCO Meet Abstr"},{"key":"BFleu2014263_CR8","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1056\/NEJMoa1400029","volume":"370","author":"JA Woyach","year":"2014","unstructured":"Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS et al. Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib. N Engl J Med 2014; 370: 2286\u20132294.","journal-title":"N Engl J Med"},{"key":"BFleu2014263_CR9","doi-asserted-by":"publisher","first-page":"2352","DOI":"10.1056\/NEJMc1402716","volume":"370","author":"RR Furman","year":"2014","unstructured":"Furman RR, Cheng S, Lu P, Setty M, Perez AR, Guo A et al. Ibrutinib resistance in chronic lymphocytic leukemia. N Engl J Med 2014; 370: 2352\u20132354.","journal-title":"N Engl J Med"},{"key":"BFleu2014263_CR10","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/leu.2013.358","volume":"28","author":"S Cheng","year":"2014","unstructured":"Cheng S, Ma J, Guo A, Lu P, Leonard JP, Coleman M et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia 2014; 28: 649\u2013657.","journal-title":"Leukemia"},{"key":"BFleu2014263_CR11","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1158\/1078-0432.CCR-09-1519","volume":"16","author":"Z Song","year":"2010","unstructured":"Song Z, Lu P, Furman RR, Leonard JP, Martin P, Tyrell L et al. Activities of SYK and PLCgamma2 predict apoptotic response of CLL cells to SRC tyrosine kinase inhibitor dasatinib. Clin Cancer Res 2010; 16: 587\u2013599.","journal-title":"Clin Cancer Res"},{"key":"BFleu2014263_CR12","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1038\/leu.2008.163","volume":"22","author":"C Yang","year":"2008","unstructured":"Yang C, Lu P, Lee FY, Chadburn A, Barrientos JC, Leonard JP et al. Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib. Leukemia 2008; 22: 1755\u20131766.","journal-title":"Leukemia"},{"key":"BFleu2014263_CR13","doi-asserted-by":"publisher","first-page":"3737","DOI":"10.4049\/jimmunol.177.6.3737","volume":"177","author":"SH Jo","year":"2006","unstructured":"Jo SH, Yang C, Miao Q, Marzec M, Wasik MA, Lu P et al. Peroxisome proliferator-activated receptor gamma promotes lymphocyte survival through its actions on cellular metabolic activities. J Immunol 2006; 177: 3737\u20133745.","journal-title":"J Immunol"},{"key":"BFleu2014263_CR14","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/leu.2008.304","volume":"23","author":"P Lu","year":"2009","unstructured":"Lu P, Yang C, Guasparri I, Harrington W, Wang YL, Cesarman E . Early events of B-cell receptor signaling are not essential for the proliferation and viability of AIDS-related lymphoma. Leukemia 2009; 23: 807\u2013810.","journal-title":"Leukemia"},{"key":"BFleu2014263_CR15","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1182\/blood-2010-05-284984","volume":"117","author":"Y Herishanu","year":"2011","unstructured":"Herishanu Y, Perez-Galan P, Liu D, Biancotto A, Pittaluga S, Vire B et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 2011; 117: 563\u2013574.","journal-title":"Blood"},{"key":"BFleu2014263_CR16","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1182\/blood-2007-04-083832","volume":"110","author":"RN Damle","year":"2007","unstructured":"Damle RN, Temburni S, Calissano C, Yancopoulos S, Banapour T, Sison C et al. CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cells. Blood 2007; 110: 3352\u20133359.","journal-title":"Blood"},{"key":"BFleu2014263_CR17","doi-asserted-by":"publisher","first-page":"6342","DOI":"10.1182\/blood-2011-02-333773","volume":"118","author":"S Cheng","year":"2011","unstructured":"Cheng S, Coffey G, Zhang XH, Shaknovich R, Song Z, Lu P et al. SYK inhibition and response prediction in diffuse large B-cell lymphoma. Blood 2011; 118: 6342\u20136352.","journal-title":"Blood"},{"key":"BFleu2014263_CR18","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1124\/dmd.107.018267","volume":"36","author":"LJ Christopher","year":"2008","unstructured":"Christopher LJ, Cui D, Wu C, Luo R, Manning JA, Bonacorsi SJ et al. Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos 2008; 36: 1357\u20131364.","journal-title":"Drug Metab Dispos"},{"key":"BFleu2014263_CR19","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1124\/jpet.113.209304","volume":"348","author":"ME Dowty","year":"2014","unstructured":"Dowty ME, Jesson MI, Ghosh S, Lee J, Meyer DM, Krishnaswami S et al. Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis. J Pharmacol Exp Ther 2014; 348: 165\u2013173.","journal-title":"J Pharmacol Exp Ther"},{"key":"BFleu2014263_CR20","doi-asserted-by":"publisher","first-page":"13283","DOI":"10.1073\/pnas.0702654104","volume":"104","author":"O Hantschel","year":"2007","unstructured":"Hantschel O, Rix U, Schmidt U, Burckstummer T, Kneidinger M, Schutze G et al. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci USA 2007; 104: 13283\u201313288.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2014263_CR21","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa1315226","volume":"370","author":"RR Furman","year":"2014","unstructured":"Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370: 997\u20131007.","journal-title":"N Engl J Med"},{"key":"BFleu2014263_CR22","doi-asserted-by":"publisher","first-page":"3390","DOI":"10.1182\/blood-2013-11-535047","volume":"123","author":"JR Brown","year":"2014","unstructured":"Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed\/refractory chronic lymphocytic leukemia. Blood 2014; 123: 3390\u20133397.","journal-title":"Blood"},{"key":"BFleu2014263_CR23","doi-asserted-by":"crossref","unstructured":"Jin F, Robeson M, Zhou H, Moyer C, Ramanathan S . Pharmacokinetics and safety of idelalisib, a novel PI3K\u03b4 inhibitor, in Japanese and Caucasian subjects. ASH Annu Meet Abstr 2013; abstract 5575.","DOI":"10.1182\/blood.V122.21.5575.5575"},{"key":"BFleu2014263_CR24","doi-asserted-by":"crossref","unstructured":"Burger JA, Landau D, Hoellenriegel J, Sougnez C, Schlesner M, Ishaque N et al. Clonal evolution in patients with chronic lymphocytic leukemia (CLL) developing resistance to BTK inhibition. ASH Annu Meet Abstr 2013; abstract 866.","DOI":"10.1182\/blood.V122.21.866.866"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/leu2014263.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2014263","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2014263.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T16:09:30Z","timestamp":1648742970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/leu2014263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,5]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,4]]}},"alternative-id":["BFleu2014263"],"URL":"https:\/\/doi.org\/10.1038\/leu.2014.263","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,5]]},"assertion":[{"value":"8 April 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2014","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2014","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 September 2014","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}