{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:16:41Z","timestamp":1790551001074,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T00:00:00Z","timestamp":1417564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004097","name":"Fondation ARC pour la recherche sur le cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004097","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Institut national du cancer INCA"},{"name":"LABEX INFLAMEX","award":["n\u00c2\u00b0 ANR11 IDEX 00502"],"award-info":[{"award-number":["n\u00c2\u00b0 ANR11 IDEX 00502"]}]},{"name":"University Paris 13"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:p>Several studies provide evidences for mantle cell lymphoma (MCL) cell survival relying on B\u2010cell receptor (BCR)\u2010mediated signalling pathways, whereas the nature of this activation is unknown. Significant progress in MCL treatment is achieved through therapies targeting BCR\u2010associated kinases, <jats:italic>i.e<\/jats:italic>., Ibrutinib and Fostamatinib, inhibitors of BTK and SYK, respectively. Our study addresses survival signals emanating from the BCR or the tumour environment and how inhibiting BCR signalling effectors might impact these survival signals. We found that BTK was constitutively activated and that SYK phosphorylation was highly increased and sustained upon BCR activation of primary MCL cells. Moreover, MCL cells from leukaemic patients secreted high amount of IL\u20101\u03b2, IL\u20106, IL\u20108 and CCL5. Activation of the BCR induced (<jats:italic>i<\/jats:italic>) cell survival, (<jats:italic>ii<\/jats:italic>) STAT3 activation and (<jats:italic>iii<\/jats:italic>) increased autocrine secretion of IL\u20101\u03b2, IL\u20106, IL\u20108, CCL5, IL\u201010, TNF\u03b1 and VEGF. Specific inhibition of BTK by Ibrutinib or SYK by Fostamatinib (R406) reversed these protective effects and decreased both basal and BCR\u2010induced autocrine cytokine secretions associated with STAT3 phosphorylation. Interestingly, targeting BTK and SYK prevented and inhibited BCR\u2010induced MCL cell adhesion to human bone marrow stromal cells (HMSCs) in short\u2010 and long\u2010term co\u2010culture. We demonstrated that BCR\u2010induced survival relies on autocrine secretion of IL\u20101\u03b2, TNF\u03b1 and CCL5 that might facilitate adhesion of MCL cells to HMSC. Treatment with Ibrutinib or Fostamatinib blocked the chemotactic signal thus increasing apoptosis.<\/jats:p>","DOI":"10.1002\/ijc.29326","type":"journal-article","created":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T08:37:44Z","timestamp":1415781464000},"page":"2761-2774","source":"Crossref","is-referenced-by-count":50,"title":["Inhibitors of <scp>BCR<\/scp> signalling interrupt the survival signal mediated by the micro\u2010environment in mantle cell lymphoma"],"prefix":"10.1002","volume":"136","author":[{"given":"Sophie","family":"Bernard","sequence":"first","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"},{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Danglade","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gardano","sequence":"additional","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Laguillier","sequence":"additional","affiliation":[{"name":"Service de Biochimie, H\u00f4pital Jean Verdier, Assistance Publique\u2013H\u00f4pitaux de Paris Bondy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Lazarian","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Roger","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Thieblemont","sequence":"additional","affiliation":[{"name":"H\u00e9matologie, H\u00f4pital Saint\u2010Louis, Assistance Publique\u2013H\u00f4pitaux de Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Marzec","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary, University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Gribben","sequence":"additional","affiliation":[{"name":"Barts Cancer Institute, Queen Mary, University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Cymbalista","sequence":"additional","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"},{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Varin\u2010Blank","sequence":"additional","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Ledoux","sequence":"additional","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Baran\u2010Marszak","sequence":"additional","affiliation":[{"name":"U978 Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Bobigny France"},{"name":"Labex Inflamex, Universit\u00e9 Paris 13 Sorbonne Paris Cit\u00e9 Bobigny France"},{"name":"Service d'H\u00e9matologie Biologique, H\u00f4pital Avicenne, Assistance Publique\u2013H\u00f4pitaux de Paris Bobigny France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,3]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"229","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Swerdlow S","year":"2008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.8435"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.42.7906"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1306220"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-236471"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208075"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2853"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2008.00748.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-011-0019-7"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05883.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-3215"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800515-MCP200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403216"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-10-185827"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.040659"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-03-212837"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4252"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-02-362624"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-396853"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011866"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404970"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.11.012"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-165068"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-11-390989"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.379"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3937"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.019745"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-02-0540"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00210"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-NB2013-172"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-482125"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2765"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-100115"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12588"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04118.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10772"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.621566"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-010-0066-1"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.21579"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190902856808"},{"key":"e_1_2_7_42_1","first-page":"2899","article-title":"Immunohistochemical detection of C\u2010kit (CD117) and vascular endothelial growth factor (VEGF) overexpression in mantle cell lymphoma","volume":"22","author":"Potti A","year":"2002","journal-title":"Anticancer Res"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2763"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.015"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.06.018"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00282-996-0241-3"},{"key":"e_1_2_7_47_1","first-page":"4419","article-title":"The role of hyaluronan and interleukin 8 in the migration of chronic lymphocytic leukemia cells within lymphoreticular tissues","volume":"59","author":"Till KJ","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(97)00248-7"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114507666409"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909086107"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708516200"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074103"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-10-4054"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29326","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.29326","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:22:16Z","timestamp":1695997336000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.29326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,3]]},"references-count":52,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6,15]]}},"alternative-id":["10.1002\/ijc.29326"],"URL":"https:\/\/doi.org\/10.1002\/ijc.29326","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,3]]}}}