{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:12:14Z","timestamp":1790673134349,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T00:00:00Z","timestamp":1525824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ligue Nationale Contre le Cancer, \u00e9quipe labellis\u00e9e Ligue"},{"name":"Comit\u00e9 Orientation Recherche Cancer en Limousin"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>More than 35\u00a0years after the Binet classification, there is still a need for simple prognostic markers in chronic lymphocytic leukemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>). Here, we studied the treatment\u2010free survival (<jats:styled-content style=\"fixed-case\">TFS<\/jats:styled-content>) impact of normal serum protein electrophoresis (<jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content>) at diagnosis. One hundred twelve patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> were analyzed. The main prognostic factors (Binet stage; lymphocytosis; <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content> mutation status; <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">BIRC<\/jats:styled-content>3<\/jats:italic> mutations; and cytogenetic abnormalities) were studied. The frequencies of <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content> mutation status, cytogenetic abnormalities, and <jats:italic><jats:styled-content style=\"fixed-case\">TP<\/jats:styled-content>53<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">SF<\/jats:styled-content>3B1<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>1,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">BIRC<\/jats:styled-content>3<\/jats:italic> mutations were not significantly different between normal and abnormal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content>. Normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> was associated with Binet stage A, nonprogressive disease for 6\u00a0months, lymphocytosis below 30\u00a0G\/L, and the absence of the <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content>3\u201021 gene rearrangement which is associated with poor prognosis. The <jats:styled-content style=\"fixed-case\">TFS<\/jats:styled-content> of patients with normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> was significantly longer than that of patients with abnormal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> (log\u2010rank test: <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0015, with 51% untreated patients at 5.6\u00a0years and a perfect plateau afterward vs. a median <jats:styled-content style=\"fixed-case\">TFS<\/jats:styled-content> at 2.64\u00a0years for abnormal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> with no plateau). Multivariate analysis using two different Cox models and bootstrapping showed that normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> was an independent good prognostic marker for either Binet stage, lymphocytosis, or <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content> mutation status. <jats:styled-content style=\"fixed-case\">TFS<\/jats:styled-content> was further increased when both normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> and mutated <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content> were present (log\u2010rank test: <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008, median not reached, plateau at 5.6\u00a0years and 66% untreated patients). A comparison with other prognostic markers suggested that normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> could reflect slowly advancing <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> disease. Altogether, our results show that a combination of normal <jats:styled-content style=\"fixed-case\">SPE<\/jats:styled-content> and mutated <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content> genes defines a subgroup of patients with <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> who evolve very slowly and who might never need treatment.<\/jats:p>","DOI":"10.1002\/cam4.1510","type":"journal-article","created":{"date-parts":[[2018,5,9]],"date-time":"2018-05-09T23:18:54Z","timestamp":1525907934000},"page":"2621-2628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Normal serum protein electrophoresis and mutated <scp>IGHV<\/scp> genes detect very slowly evolving chronic lymphocytic leukemia patients"],"prefix":"10.1002","volume":"7","author":[{"given":"Jasmine","family":"Chauzeix","sequence":"first","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"},{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Pierre","family":"Lafor\u00eat","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Deveza","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Crowther","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Marcellaud","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco","family":"Derouault","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges EA6309  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Sophie","family":"Lia","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges EA6309  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Boyer","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Bargues","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Olombel","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"},{"name":"Immunologie Centre Hospitalier Universitaire de Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Jaccard","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"},{"name":"H\u00e9matologie Clinique et Th\u00e9rapie Cellulaire Centre Hospitalier Universitaire de Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-2454","authenticated-orcid":false,"given":"Jean","family":"Feuillard","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"},{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gachard","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"},{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rizzo","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Biologique Centre Hospitalier Universitaire de Limoges  Limoges France"},{"name":"Facult\u00e9 de M\u00e9decine de Limoges UMR CNRS 7276 CRIBL  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,9]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"WHO classification of tumours of haematopoietic and lymphoid tissues","author":"Swerdlow S. H.","year":"2008"},{"key":"e_1_2_7_3_1","first-page":"2188","article-title":"2016 revision of the WHO classification of lymphoid neoplasms","volume":"58","author":"Tamaru J.\u2010I.","year":"2017","journal-title":"Rinsho Ketsueki"},{"key":"e_1_2_7_4_1","first-page":"1640","article-title":"The immunological profile of B\u2010cell disorders and proposal of a scoring system for the diagnosis of CLL","volume":"8","author":"Matutes E.","year":"1994","journal-title":"Leukemia"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/108.4.378"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19810701)48:1<198::AID-CNCR2820480131>3.0.CO;2-V"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V46.2.219.219"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-06-288274"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1840"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.6.1848"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-08-373159"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22293"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-458265"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.585529"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2017.1323271"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24826"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.783913"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.11622"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-567388"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.198"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29438"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2006.11.001"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2010.12.005"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2016.1142082"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2016.1170830"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.257"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404727"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23494"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.028779"},{"key":"e_1_2_7_30_1","unstructured":"Coordonn\u00e9 par Andrew Kramar et Simone Mathoulin\u2010P\u00e9lissier.M\u00e9thodes biostatistiques appliqu\u00e9es \u00e0 la recherche clinique en canc\u00e9rologie. Available athttp:\/\/www.jle.com\/fr\/ouvrages\/e-docs\/methodes_biostatistiques_appliquees_a_la_recherche_clinique_en_cancerologie_290431\/ouvrage.phtml(accessed 17 October 2017)."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.134510"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30029-8"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15015"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24660"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402731"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.1510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.1510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T12:36:01Z","timestamp":1754915761000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.1510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,9]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/cam4.1510"],"URL":"https:\/\/doi.org\/10.1002\/cam4.1510","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,9]]},"assertion":[{"value":"2017-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}