{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:45:28Z","timestamp":1790009128488,"version":"4.0.1"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010552","name":"Departament de Salut, Generalitat de Catalunya","doi-asserted-by":"publisher","award":["SLT002\u201016\u201000350"],"award-info":[{"award-number":["SLT002\u201016\u201000350"]}],"id":[{"id":"10.13039\/501100010552","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["CB16\/12\/00225"],"award-info":[{"award-number":["CB16\/12\/00225"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["CB16\/12\/00334"],"award-info":[{"award-number":["CB16\/12\/00334"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:p>The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been shown to be highly effective in patients with chronic lymphocytic leukemia (CLL) and is approved for CLL treatment. Unfortunately, resistance and intolerance to ibrutinib has been observed in several studies, opening the door for more specific BTK inhibitors. CC\u2010292 (spebrutinib) is a BTK inhibitor with increased specificity for BTK and less inhibition of other kinases. Our <jats:italic>in vitro<\/jats:italic> studies showed that CC\u2010292 potently inhibited B\u2010cell receptor signaling, activation, proliferation and chemotaxis of CLL cells. In <jats:italic>in vivo<\/jats:italic> studies using the adoptive transfer TCL1 mouse model of CLL, CC\u2010292 reduced tumor load and normalized tumor\u2010associated expansion of T cells and monocytes, while not affecting T cell function. Importantly, the combination of CC\u2010292 and bendamustine impaired CLL cell proliferation <jats:italic>in vivo<\/jats:italic> and enhanced the control of CLL progression. Our results demonstrate that CC\u2010292 is a specific BTK inhibitor with promising performance in combination with bendamustine in CLL. Further clinical trials are warranted to investigate the therapeutic efficacy of this combination regimen.<\/jats:p>","DOI":"10.1002\/ijc.32010","type":"journal-article","created":{"date-parts":[[2018,11,23]],"date-time":"2018-11-23T10:49:40Z","timestamp":1542970180000},"page":"2762-2773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Selective BTK inhibition improves bendamustine therapy response and normalizes immune effector functions in chronic lymphocytic leukemia"],"prefix":"10.1002","volume":"144","author":[{"given":"Eriong","family":"Lee\u2010Verg\u00e9s","sequence":"first","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bola S.","family":"Hanna","sequence":"additional","affiliation":[{"name":"Molecular Genetics German Cancer Research Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haniyeh","family":"Yazdanparast","sequence":"additional","affiliation":[{"name":"Molecular Genetics German Cancer Research Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanina","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Leonor","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"Gir\u00f3","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Vidal\u2010Crespo","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Rosich","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Amador","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Aymerich","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematopathology Unit, Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neus","family":"Villamor","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematopathology Unit, Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Delgado","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematology Department Hospital Clinic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lichter","sequence":"additional","affiliation":[{"name":"Molecular Genetics German Cancer Research Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"P\u00e9rez\u2010Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f2nica","family":"L\u00f3pez\u2010Guerra","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematopathology Unit, Hospital Cl\u00ednic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u00edas","family":"Campo","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematopathology Unit, Hospital Cl\u00ednic  Barcelona Spain"},{"name":"University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Seiffert","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7486-8484","authenticated-orcid":false,"given":"Dolors","family":"Colomer","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red C\u00e1ncer (CIBERONC)  Barcelona Spain"},{"name":"Hematopathology Unit, Hospital Cl\u00ednic  Barcelona Spain"},{"name":"University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.07.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2001\/28962"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00741.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-04-585067"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30051-1"},{"key":"e_1_2_7_7_1","first-page":"1","article-title":"Bendamustine: mechanism of action and clinical data","volume":"9","author":"Cheson BD","year":"2011","journal-title":"Clin Adv Hematol Oncol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2014.08.003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-0388"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.33.8061"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.2688"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6685"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/2040620717699365"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509388"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.175"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215637"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30212-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1400029"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-603670"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.777837"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.203489"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.140806"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1403189"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102181599"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.305"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-01-622936"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(03)00265-5"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0827"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-507947"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89756"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.111"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0250-6"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-328484"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.11.3658"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.69"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.168930"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509981"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2011.03.003"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00465-9"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2017.1350166"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2017.06.023"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0463"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-606038"},{"key":"e_1_2_7_45_1","first-page":"385","article-title":"IL\u201010 receptor deficiency aggravates exhaustion of CD8+ T\u2010cells and impedes their control of chronic lymphocytic leukemia","volume":"130","author":"Hanna BS","year":"2017","journal-title":"Blood"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-01-547869"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1965"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.32010","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32010","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.32010","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.32010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T15:08:25Z","timestamp":1694358505000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.32010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,16]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/ijc.32010"],"URL":"https:\/\/doi.org\/10.1002\/ijc.32010","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,16]]},"assertion":[{"value":"2018-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}