{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:08:41Z","timestamp":1792069721288,"version":"4.4.0"},"reference-count":89,"publisher":"American Society of Hematology","issue":"13","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bruton tyrosine kinase inhibitors (BTKi) have significantly changed the treatment landscape for patients with B-cell malignancies, including chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Unfortunately, patients with BTKi-resistant disease have shortened survival. Clinical and molecular risk factors, such as number of prior therapies and presence of TP53 mutations, can be used to predict patients at the highest risk of developing BTKi resistance. Many mechanisms of BTKi resistance have been reported with mutations in BTK and phospholipase C \u03b32 supported with the most data. The introduction of venetoclax has lengthened the survival of patients with BTKi-resistant disease. Ongoing clinical trials with promising treatment modalities, such as next-generation BTKi and chimeric antigen receptor T-cell therapy, have reported promising efficacy in patients with BTKi-resistant disease. Continued research focusing on resistance mechanisms and methods of how to circumvent resistance is needed to further prolong the survival of patients with BTKi-resistant B-cell malignancies.<\/jats:p>","DOI":"10.1182\/blood.2020006783","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T17:55:17Z","timestamp":1627494917000},"page":"1099-1109","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["Resistance to Bruton tyrosine kinase inhibitors: the Achilles heel of their success story in lymphoid malignancies"],"prefix":"10.1182","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9188-5008","authenticated-orcid":false,"given":"Deborah M.","family":"Stephens","sequence":"first","affiliation":[{"name":"Division of Hematology and Hematologic Malignancies, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John C.","family":"Byrd","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"51","key":"2021100515301828100_B1","doi-asserted-by":"crossref","first-page":"36953","DOI":"10.1074\/jbc.M707682200","article-title":"Signaling by Toll-like receptors 8 and 9 requires Bruton\u2019s tyrosine kinase","volume":"282","author":"Doyle","year":"2007","journal-title":"J Biol Chem."},{"issue":"10","key":"2021100515301828100_B2","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1084\/jem.20011866","article-title":"The B cell antigen receptor controls integrin activity through Btk and PLCgamma2","volume":"198","author":"Spaargaren","year":"2003","journal-title":"J Exp Med."},{"issue":"6554","key":"2021100515301828100_B3","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/378298a0","article-title":"Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk","volume":"378","author":"Turner","year":"1995","journal-title":"Nature."},{"issue":"1","key":"2021100515301828100_B4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1128\/MCB.00468-10","article-title":"Requirement for class II phosphoinositide 3-kinase C2alpha in maintenance of glomerular structure and function","volume":"31","author":"Harris","year":"2011","journal-title":"Mol Cell Biol."},{"issue":"3","key":"2021100515301828100_B5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/1074-7613(95)90114-0","article-title":"Defective B cell development and function in Btk-deficient mice","volume":"3","author":"Khan","year":"1995","journal-title":"Immunity."},{"issue":"16","key":"2021100515301828100_B6","doi-asserted-by":"crossref","first-page":"4313","DOI":"10.1182\/blood-2011-06-338855","article-title":"B-cell receptor signaling in chronic lymphocytic leukemia","volume":"118","author":"Stevenson","year":"2011","journal-title":"Blood."},{"issue":"3","key":"2021100515301828100_B7","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/j.seminhematol.2014.05.003","article-title":"The meaning and relevance of B-cell receptor structure and function in chronic lymphocytic leukemia","volume":"51","author":"Stevenson","year":"2014","journal-title":"Semin Hematol."},{"issue":"7","key":"2021100515301828100_B8","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1182\/blood-2011-07-367417","article-title":"Mechanisms and clinical significance of BIM phosphorylation in chronic lymphocytic leukemia","volume":"119","author":"Paterson","year":"2012","journal-title":"Blood."},{"issue":"1","key":"2021100515301828100_B9","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1182\/blood-2011-07-370403","article-title":"Surface IgM stimulation induces MEK1\/2-dependent MYC expression in chronic lymphocytic leukemia cells","volume":"119","author":"Krysov","year":"2012","journal-title":"Blood."},{"issue":"3","key":"2021100515301828100_B10","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11899-019-00512-0","article-title":"Targeting BTK in CLL: beyond ibrutinib","volume":"14","author":"Bond","year":"2019","journal-title":"Curr Hematol Malig Rep."},{"issue":"1","key":"2021100515301828100_B11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s10020-018-0001-1","article-title":"Critical molecular pathways in CLL therapy","volume":"24","author":"Ferrer","year":"2018","journal-title":"Mol Med."},{"issue":"12","key":"2021100515301828100_B12","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.it.2013.07.002","article-title":"B cell receptor signaling in chronic lymphocytic leukemia","volume":"34","author":"Burger","year":"2013","journal-title":"Trends Immunol."},{"issue":"7415","key":"2021100515301828100_B13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nature11309","article-title":"Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling","volume":"489","author":"D\u00fchren-von Minden","year":"2012","journal-title":"Nature."},{"issue":"4","key":"2021100515301828100_B14","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/leu.2015.316","article-title":"BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia","volume":"30","author":"Chen","year":"2016","journal-title":"Leukemia."},{"issue":"3","key":"2021100515301828100_B15","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1056\/NEJMoa1400376","article-title":"Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia","volume":"371","author":"Byrd","year":"2014","journal-title":"N Engl J Med."},{"issue":"25","key":"2021100515301828100_B16","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N Engl J Med."},{"issue":"5","key":"2021100515301828100_B17","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1056\/NEJMoa1817073","article-title":"Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia","volume":"381","author":"Shanafelt","year":"2019","journal-title":"N Engl J Med."},{"issue":"26","key":"2021100515301828100_B18","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1056\/NEJMoa1812836","article-title":"Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL","volume":"379","author":"Woyach","year":"2018","journal-title":"N Engl J Med."},{"issue":"10020","key":"2021100515301828100_B19","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/S0140-6736(15)00667-4","article-title":"Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study","volume":"387","author":"Dreyling","year":"2016","journal-title":"Lancet."},{"issue":"25","key":"2021100515301828100_B20","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.1056\/NEJMoa1802917","article-title":"Phase 3 trial of ibrutinib plus rituximab in Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"378","author":"Dimopoulos","year":"2018","journal-title":"N Engl J Med."},{"issue":"8","key":"2021100515301828100_B21","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1038\/nm.3884","article-title":"Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma","volume":"21","author":"Wilson","year":"2015","journal-title":"Nat Med."},{"issue":"10232","key":"2021100515301828100_B22","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0140-6736(20)30262-2","article-title":"Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial","volume":"395","author":"Sharman","year":"2020","journal-title":"Lancet."},{"issue":"25","key":"2021100515301828100_B23","doi-asserted-by":"crossref","first-page":"2849","DOI":"10.1200\/JCO.19.03355","article-title":"ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia","volume":"38","author":"Ghia","year":"2020","journal-title":"J Clin Oncol."},{"issue":"16","key":"2021100515301828100_B24","doi-asserted-by":"crossref","first-page":"4216","DOI":"10.1158\/1078-0432.CCR-19-3703","article-title":"Treatment of patients with relapsed or refractory mantle-cell lymphoma with zanubrutinib, a selective inhibitor of Bruton\u2019s tyrosine kinase","volume":"26","author":"Song","year":"2020","journal-title":"Clin Cancer Res."},{"issue":"18","key":"2021100515301828100_B25","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1182\/blood.2020006844","article-title":"A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenstr\u00f6m macroglobulinemia: the ASPEN study","volume":"136","author":"Tam","year":"2020","journal-title":"Blood."},{"issue":"23","key":"2021100515301828100_B26","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.1182\/blood-2011-01-328484","article-title":"Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765","volume":"117","author":"Herman","year":"2011","journal-title":"Blood."},{"issue":"4","key":"2021100515301828100_B27","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1509981","article-title":"Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia","volume":"374","author":"Byrd","year":"2016","journal-title":"N Engl J Med."},{"issue":"11","key":"2021100515301828100_B28","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1182\/blood.2019001160","article-title":"Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL","volume":"134","author":"Tam","year":"2019","journal-title":"Blood."},{"issue":"11","key":"2021100515301828100_B29","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1158\/1078-0432.CCR-16-0463","article-title":"The Bruton tyrosine kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia","volume":"23","author":"Herman","year":"2017","journal-title":"Clin Cancer Res."},{"issue":"1","key":"2021100515301828100_B30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1001\/jamaoncol.2014.218","article-title":"Etiology of ibrutinib therapy discontinuation and outcomes in patients with chronic lymphocytic leukemia","volume":"1","author":"Maddocks","year":"2015","journal-title":"JAMA Oncol."},{"issue":"13","key":"2021100515301828100_B31","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1182\/blood-2014-09-603670","article-title":"Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib","volume":"125","author":"Jain","year":"2015","journal-title":"Blood."},{"issue":"15","key":"2021100515301828100_B32","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1158\/1078-0432.CCR-19-2856","article-title":"Ibrutinib treatment for first-line and relapsed\/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib\/II PCYC-1102 study","volume":"26","author":"Byrd","year":"2020","journal-title":"Clin Cancer Res."},{"key":"2021100515301828100_B33","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2019-127674","article-title":"Resistance to acalabrutinib in CLL is mediated primarily by BTK mutations [abstract]","volume":"134","author":"Woyach","year":"2019","journal-title":"Blood."},{"issue":"1","key":"2021100515301828100_B34","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S1470-2045(17)30909-9","article-title":"Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial","volume":"19","author":"Jones","year":"2018","journal-title":"Lancet Oncol."},{"issue":"11","key":"2021100515301828100_B35","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.1080\/10428194.2019.1602268","article-title":"Rapid disease progression following discontinuation of ibrutinib in patients with chronic lymphocytic leukemia treated in routine clinical practice","volume":"60","author":"Hampel","year":"2019","journal-title":"Leuk Lymphoma."},{"issue":"13","key":"2021100515301828100_B36","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1200\/JCO.2016.70.2282","article-title":"BTKC481S-mediated resistance to ibrutinib in chronic lymphocytic leukemia","volume":"35","author":"Woyach","year":"2017","journal-title":"J Clin Oncol."},{"issue":"1","key":"2021100515301828100_B37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/leu.2017.175","article-title":"Extended follow-up and impact of high-risk prognostic factors from the phase 3 RESONATE study in patients with previously treated CLL\/SLL","volume":"32","author":"Brown","year":"2018","journal-title":"Leukemia."},{"issue":"5","key":"2021100515301828100_B38","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1056\/NEJMc2005943","article-title":"Ibrutinib for chronic lymphocytic leukemia with TP53 alterations","volume":"383","author":"Ahn","year":"2020","journal-title":"N Engl J Med."},{"issue":"12","key":"2021100515301828100_B39","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1038\/sj.leu.2404935","article-title":"Comprehensive genetic characterization of CLL: a study on 506 cases analysed with chromosome banding analysis, interphase FISH, IgV(H) status and immunophenotyping","volume":"21","author":"Haferlach","year":"2007","journal-title":"Leukemia."},{"issue":"4","key":"2021100515301828100_B40","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/leu.2014.297","article-title":"Detailed analysis of therapy-driven clonal evolution of TP53 mutations in chronic lymphocytic leukemia","volume":"29","author":"Malcikova","year":"2015","journal-title":"Leukemia."},{"issue":"2","key":"2021100515301828100_B41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.leukres.2013.10.019","article-title":"Clonal evolution in chronic lymphocytic leukemia detected by fluorescence in situ hybridization and conventional cytogenetics after stimulation with CpG oligonucleotides and interleukin-2: a prospective analysis","volume":"38","author":"Brejcha","year":"2014","journal-title":"Leuk Res."},{"issue":"6","key":"2021100515301828100_B42","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1200\/JCO.20.00979","article-title":"Prediction of outcome in patients with chronic lymphocytic leukemia treated with ibrutinib: development and validation of a four-factor prognostic model","volume":"39","author":"Ahn","year":"2021","journal-title":"J Clin Oncol."},{"issue":"7","key":"2021100515301828100_B43","doi-asserted-by":"crossref","first-page":"e366","DOI":"10.1016\/S2352-3026(19)30085-7","article-title":"Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations","volume":"6","author":"Soumerai","year":"2019","journal-title":"Lancet Haematol."},{"issue":"3","key":"2021100515301828100_B44","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/bjh.15613","article-title":"Unravelling the suboptimal response of TP53-mutated chronic lymphocytic leukaemia to ibrutinib","volume":"184","author":"Guarini","year":"2019","journal-title":"Br J Haematol."},{"issue":"26","key":"2021100515301828100_B45","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1056\/NEJMx140036","article-title":"Ibrutinib resistance in chronic lymphocytic leukemia [published correction appears in","volume":"370","author":"Furman","year":"2014","journal-title":"N Engl J Med."},{"issue":"24","key":"2021100515301828100_B46","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1056\/NEJMoa1400029","article-title":"Resistance mechanisms for the Bruton\u2019s tyrosine kinase inhibitor ibrutinib","volume":"370","author":"Woyach","year":"2014","journal-title":"N Engl J Med."},{"issue":"38","key":"2021100515301828100_B47","doi-asserted-by":"crossref","first-page":"13906","DOI":"10.1073\/pnas.1409362111","article-title":"Evolution of ibrutinib resistance in chronic lymphocytic leukemia (CLL)","volume":"111","author":"Komarova","year":"2014","journal-title":"Proc Natl Acad Sci USA."},{"issue":"11","key":"2021100515301828100_B48","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1182\/blood-2016-06-719294","article-title":"Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia","volume":"129","author":"Ahn","year":"2017","journal-title":"Blood."},{"issue":"18","key":"2021100515301828100_B49","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1182\/blood-2017-01-761726","article-title":"Acquired mutations associated with ibrutinib resistance in Waldenstr\u00f6m macroglobulinemia","volume":"129","author":"Xu","year":"2017","journal-title":"Blood."},{"issue":"9","key":"2021100515301828100_B50","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1158\/2159-8290.CD-14-0098","article-title":"Cell-cycle reprogramming for PI3K inhibition overrides a relapse-specific C481S BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma","volume":"4","author":"Chiron","year":"2014","journal-title":"Cancer Discov."},{"issue":"4","key":"2021100515301828100_B51","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1182\/bloodadvances.2018029058","article-title":"Resistance mechanism for ibrutinib in marginal zone lymphoma","volume":"3","author":"Epperla","year":"2019","journal-title":"Blood Adv."},{"issue":"10","key":"2021100515301828100_B52","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1021\/acschembio.6b00480","article-title":"Battling Btk mutants with noncovalent inhibitors that overcome Cys481 and Thr474 mutations","volume":"11","author":"Johnson","year":"2016","journal-title":"ACS Chem Biol."},{"issue":"42","key":"2021100515301828100_B53","doi-asserted-by":"crossref","first-page":"68833","DOI":"10.18632\/oncotarget.11932","article-title":"Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL","volume":"7","author":"Sharma","year":"2016","journal-title":"Oncotarget."},{"issue":"12","key":"2021100515301828100_B54","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1182\/bloodadvances.2016003632","article-title":"Clonal evolution underlying leukemia progression and Richter transformation in patients with ibrutinib-relapsed CLL","volume":"1","author":"Kadri","year":"2017","journal-title":"Blood Adv."},{"issue":"1","key":"2021100515301828100_B55","doi-asserted-by":"crossref","first-page":"11589","DOI":"10.1038\/ncomms11589","article-title":"Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition","volume":"7","author":"Burger","year":"2016","journal-title":"Nat Commun."},{"issue":"9","key":"2021100515301828100_B56","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1182\/blood-2005-05-2013","article-title":"Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes","volume":"106","author":"Rubio-Moscardo","year":"2005","journal-title":"Blood."},{"issue":"6","key":"2021100515301828100_B57","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1111\/bjh.16463","article-title":"Genomic evolution of ibrutinib-resistant clones in Waldenstr\u00f6m macroglobulinaemia","volume":"189","author":"Jim\u00e9nez","year":"2020","journal-title":"Br J Haematol."},{"issue":"4","key":"2021100515301828100_B58","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/cncr.31831","article-title":"Targeted multigene deep sequencing of Bruton tyrosine kinase inhibitor-resistant chronic lymphocytic leukemia with disease progression and Richter transformation","volume":"125","author":"Kanagal-Shamanna","year":"2019","journal-title":"Cancer."},{"issue":"2","key":"2021100515301828100_B59","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1182\/blood-2017-09-804641","article-title":"Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial","volume":"131","author":"Bartlett","year":"2018","journal-title":"Blood."},{"issue":"25","key":"2021100515301828100_B60","doi-asserted-by":"crossref","first-page":"38180","DOI":"10.18632\/oncotarget.9500","article-title":"Genetic heterogeneity in primary and relapsed mantle cell lymphomas: impact of recurrent CARD11 mutations","volume":"7","author":"Wu","year":"2016","journal-title":"Oncotarget."},{"issue":"18","key":"2021100515301828100_B61","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1182\/blood-2017-10-811752","article-title":"BTKCys481Ser drives ibrutinib resistance via ERK1\/2 and protects BTKwild-type MYD88-mutated cells by a paracrine mechanism","volume":"131","author":"Chen","year":"2018","journal-title":"Blood."},{"issue":"21","key":"2021100515301828100_B62","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V122.21.866.866","article-title":"Clonal evolution in patients with chronic lymphocytic leukemia (CLL) developing resistance to BTK inhibition [abstract]","volume":"122","author":"Burger","year":"2013","journal-title":"Blood."},{"issue":"4","key":"2021100515301828100_B63","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/leu.2014.263","article-title":"Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors","volume":"29","author":"Cheng","year":"2015","journal-title":"Leukemia."},{"issue":"11","key":"2021100515301828100_B64","doi-asserted-by":"crossref","first-page":"e452","DOI":"10.3324\/haematol.2017.172627","article-title":"CXCL13 levels are elevated in patients with Waldenstr\u00f6m macroglobulinemia, and are predictive of major response to ibrutinib","volume":"102","author":"Vos","year":"2017","journal-title":"Haematologica."},{"issue":"15","key":"2021100515301828100_B65","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1501548","article-title":"Ibrutinib in previously treated Waldenstr\u00f6m\u2019s macroglobulinemia","volume":"372","author":"Treon","year":"2015","journal-title":"N Engl J Med."},{"issue":"6","key":"2021100515301828100_B66","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/bjh.12974","article-title":"Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells","volume":"166","author":"Ma","year":"2014","journal-title":"Br J Haematol."},{"issue":"1","key":"2021100515301828100_B67","doi-asserted-by":"crossref","first-page":"14920","DOI":"10.1038\/ncomms14920","article-title":"Unification of de novo and acquired ibrutinib resistance in mantle cell lymphoma","volume":"8","author":"Zhao","year":"2017","journal-title":"Nat Commun."},{"issue":"1","key":"2021100515301828100_B68","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nm.3435","article-title":"Pharmacological and genomic profiling identifies NF-\u03baB-targeted treatment strategies for mantle cell lymphoma","volume":"20","author":"Rahal","year":"2014","journal-title":"Nat Med."},{"issue":"2","key":"2021100515301828100_B69","doi-asserted-by":"crossref","first-page":"448","DOI":"10.3324\/haematol.2019.219550","article-title":"Biological and clinical implications of BIRC3 mutations in chronic lymphocytic leukemia","volume":"105","author":"Diop","year":"2020","journal-title":"Haematologica."},{"issue":"1","key":"2021100515301828100_B70","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s41591-018-0243-z","article-title":"Dynamic molecular monitoring reveals that SWI-SNF mutations mediate resistance to ibrutinib plus venetoclax in mantle cell lymphoma","volume":"25","author":"Agarwal","year":"2019","journal-title":"Nat Med."},{"issue":"6769","key":"2021100515301828100_B71","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/35000501","article-title":"Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling","volume":"403","author":"Alizadeh","year":"2000","journal-title":"Nature."},{"issue":"7718","key":"2021100515301828100_B72","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41586-018-0290-0","article-title":"A multiprotein supercomplex controlling oncogenic signalling in lymphoma","volume":"560","author":"Phelan","year":"2018","journal-title":"Nature."},{"issue":"11","key":"2021100515301828100_B73","doi-asserted-by":"crossref","first-page":"6092","DOI":"10.1073\/pnas.1921187117","article-title":"Regulation of B cell receptor-dependent NF-\u03baB signaling by the tumor suppressor KLHL14","volume":"117","author":"Choi","year":"2020","journal-title":"Proc Natl Acad Sci USA."},{"key":"2021100515301828100_B74","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2020-141363","article-title":"BCL10 gain-of-function mutations aberrantly induce canonical and non-canonical NF-Kb activation and resistance to ibrutinib in ABC-DLBCL [abstract 2-3]","volume":"136","author":"Xia","year":"2020","journal-title":"Blood."},{"issue":"5","key":"2021100515301828100_B75","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1093\/annonc\/mdx031","article-title":"Optimal sequencing of ibrutinib, idelalisib, and venetoclax in chronic lymphocytic leukemia: results from a multicenter study of 683 patients","volume":"28","author":"Mato","year":"2017","journal-title":"Ann Oncol."},{"issue":"24","key":"2021100515301828100_B76","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1182\/blood-2014-07-587279","article-title":"IPI-145 antagonizes intrinsic and extrinsic survival signals in chronic lymphocytic leukemia cells","volume":"124","author":"Dong","year":"2014","journal-title":"Blood."},{"issue":"1","key":"2021100515301828100_B77","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1182\/blood-2015-02-626846","article-title":"Hypermorphic mutation of phospholipase C, \u03b32 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation","volume":"126","author":"Liu","year":"2015","journal-title":"Blood."},{"issue":"21","key":"2021100515301828100_B78","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V124.21.3335.3335","article-title":"Clinical activity of duvelisib (IPI-145), a phosphoinositide-3-kinase-\u03b4,\u03b3 inhibitor, in patients previously treated with ibrutinib [abstract]","volume":"124","author":"Porcu","year":"2014","journal-title":"Blood."},{"key":"2021100515301828100_B79","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2019-127260","article-title":"Final results of phase 1, dose escalation study evaluating ARQ 531 in patients with relapsed or refractory B-cell lymphoid malignancies [abstract]","volume":"134","author":"Woyach","year":"2019","journal-title":"Blood."},{"key":"2021100515301828100_B80","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2020-134970","article-title":"LOXO-305, a next generation, highly selective, non-covalent BTK inhibitor in previously treated CLL\/SLL: results from the phase 1\/2 BRUIN Study [abstract 35-37]","volume":"136","author":"Mato","year":"2020","journal-title":"Blood."},{"issue":"16","key":"2021100515301828100_B81","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1182\/bloodadvances.2020001956","article-title":"Allogeneic stem cell transplantation for chronic lymphocytic leukemia in the era of novel agents","volume":"4","author":"Roeker","year":"2020","journal-title":"Blood Adv."},{"issue":"12","key":"2021100515301828100_B82","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1016\/j.bbmt.2016.09.013","article-title":"Clinical practice recommendations for use of allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia on behalf of the guidelines committee of the American Society for Blood and Marrow Transplantation","volume":"22","author":"Kharfan-Dabaja","year":"2016","journal-title":"Biol Blood Marrow Transplant."},{"issue":"26","key":"2021100515301828100_B83","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1200\/JCO.2017.72.8519","article-title":"Durable molecular remissions in chronic lymphocytic leukemia treated with CD19-specific chimeric antigen receptor-modified T cells after failure of ibrutinib","volume":"35","author":"Turtle","year":"2017","journal-title":"J Clin Oncol."},{"issue":"19","key":"2021100515301828100_B84","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1182\/blood.2019002936","article-title":"Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure","volume":"135","author":"Gauthier","year":"2020","journal-title":"Blood."},{"key":"2021100515301828100_B85","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2020-140491","article-title":"Updated follow-up of patients with relapsed\/refractory chronic lymphocytic leukemia\/small lymphocytic lymphoma treated with lisocabtagene maraleucel in the phase 1 monotherapy cohort of transcend CLL 004, including high-risk and ibrutinib-treated patients [abstract]","volume":"136","author":"Siddiqi","year":"2020","journal-title":"Blood."},{"issue":"303","key":"2021100515301828100_B86","doi-asserted-by":"crossref","first-page":"303ra139","DOI":"10.1126\/scitranslmed.aac5415","article-title":"Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia","volume":"7","author":"Porter","year":"2015","journal-title":"Sci Transl Med."},{"issue":"32","key":"2021100515301828100_B87","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.1200\/JCO.20.01467","article-title":"Long-term follow-up of anti-CD19 chimeric antigen receptor T-cell therapy","volume":"38","author":"Cappell","year":"2020","journal-title":"J Clin Oncol."},{"issue":"6","key":"2021100515301828100_B88","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1056\/NEJMoa1910607","article-title":"Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors","volume":"382","author":"Liu","year":"2020","journal-title":"N Engl J Med."},{"issue":"4","key":"2021100515301828100_B89","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/nrc3702","article-title":"Targeting Bruton\u2019s tyrosine kinase in B cell malignancies","volume":"14","author":"Hendriks","year":"2014","journal-title":"Nat Rev Cancer."}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/138\/13\/1099\/1826060\/bloodbld2020006783c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/138\/13\/1099\/1826060\/bloodbld2020006783c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:21:47Z","timestamp":1633623707000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/138\/13\/1099\/476466\/Resistance-to-Bruton-tyrosine-kinase-inhibitors"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":89,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2021,9,30]]}},"URL":"https:\/\/doi.org\/10.1182\/blood.2020006783","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]}}}