{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:56:43Z","timestamp":1790690203407,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004099","name":"Ligue Contre le Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Mutational complexity or tumor mutational burden (TMB) influences the course of chronic lymphocytic leukemia (CLL). However, this information is not routinely used because TMB is usually obtained from whole genome or exome, or from large gene panel high\u2010throughput sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we used the C\u2010Harrel concordance index to determine the minimum panel of genes for which mutations predict treatment\u2010free survival (TFS) as well as large resequencing panels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An eight gene estimator was defined encompassing <jats:italic>ATM<\/jats:italic>, <jats:italic>SF3B1<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>BIRC3<\/jats:italic>, <jats:italic>XPO1<\/jats:italic>, <jats:italic>MYD88<\/jats:italic>, <jats:italic>TNFAIP3<\/jats:italic>, and <jats:italic>TP53<\/jats:italic>. TMB estimated from either a large panel of genes or the eight gene estimator was increased in treated patients or in those with a short TFS (&lt;2\u00a0years), unmutated <jats:italic>IGHV<\/jats:italic> gene or with an unfavorable karyotype. Being an independent prognostic parameter, any mutation in the eight gene estimator predicted a shorter TFS better than Binet stage and <jats:italic>IGHV<\/jats:italic> mutational status among patients with an apparently non\u2010progressive disease (TFS &gt;6\u00a0months). Strikingly, the eight gene estimator was also highly informative for patients with Binet stage A CLL or with a good prognosis karyotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that the eight gene estimator, that is easily achievable by high\u2010throughput resequencing, brings robust and valuable information that predicts evolution of untreated patients at diagnosis better than any other parameter.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13435","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T21:06:46Z","timestamp":1608152806000},"page":"683-692","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A reduced panel of eight genes (<i>ATM<\/i>, <i>SF3B1<\/i>, <i>NOTCH1<\/i>, <i>BIRC3<\/i>, <i>XPO1<\/i>, <i>MYD88<\/i>, <i>TNFAIP3<\/i>, and <i>TP53<\/i>) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8283-6295","authenticated-orcid":false,"given":"Jasmine","family":"Chauzeix","sequence":"first","affiliation":[{"name":"Laboratoire d'H\u00e9matologie et UMR CNRS 7276\/INSERM 1262 CRIBL Centre de Biologie et de Recherche en Sant\u00e9 CHU et Universit\u00e9 de Limoges Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Pastoret","sequence":"additional","affiliation":[{"name":"Inserm MICMAC \u2010 UMR_S 1236 CHU Rennes Universit\u00e9 Rennes 1 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Donaty","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie et UMR CNRS 7276\/INSERM 1262 CRIBL Centre de Biologie et de Recherche en Sant\u00e9 CHU et Universit\u00e9 de Limoges Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Gachard","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie et UMR CNRS 7276\/INSERM 1262 CRIBL Centre de Biologie et de Recherche en Sant\u00e9 CHU et Universit\u00e9 de Limoges Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Fest","sequence":"additional","affiliation":[{"name":"Inserm MICMAC \u2010 UMR_S 1236 CHU Rennes Universit\u00e9 Rennes 1 Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Feuillard","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie et UMR CNRS 7276\/INSERM 1262 CRIBL Centre de Biologie et de Recherche en Sant\u00e9 CHU et Universit\u00e9 de Limoges Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie et UMR CNRS 7276\/INSERM 1262 CRIBL Centre de Biologie et de Recherche en Sant\u00e9 CHU et Universit\u00e9 de Limoges Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,16]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"SwerdlowSH.WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues: \u2026 Reflects the Views of a Working Group That Convened for an Editorial and Consensus Conference at the International Agency for Research on Cancer (IARC) Lyon October 25 \u2010 27 2007.4th edn. 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