{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:39:04Z","timestamp":1791517144098,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T00:00:00Z","timestamp":1657670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["21198"],"award-info":[{"award-number":["21198"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009647","name":"Ministry of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009647","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Richter syndrome (RS) is mostly due to the direct transformation of the chronic lymphocytic leukaemia (CLL) clone, as documented by the same immunoglobulin heavy\u2010chain variable region (IGHV) rearrangement in both CLL and RS cells. In rare cases characterized by a better outcome, the RS clone harbours a different IGHV rearrangement compared to the CLL phase. We investigated the CLL phase of clonally unrelated RS to test whether the RS clone was already identifiable prior to clinicopathologic transformation, albeit undetectable by conventional approaches. CLL cells of eight patients with unrelated RS were subjected to an ultra\u2010deep next\u2010generation sequencing (NGS) approach with a sensitivity of 10<jats:sup>\u22126<\/jats:sup>. In 7\/8 cases, the RS rearrangement was not identified in the CLL phase. In one case, the RS clone was identified at a very low frequency in the CLL phase, conceivably due to the concomitance of CLL sampling and RS diagnosis. Targeted resequencing revealed that clonally unrelated RS carries genetic lesions primarily affecting the <jats:italic>TP53<\/jats:italic>, <jats:italic>MYC<\/jats:italic>, <jats:italic>ATM<\/jats:italic> and <jats:italic>NOTCH1<\/jats:italic> genes. Conversely, mutations frequently involved in de novo diffuse large B\u2010cell lymphoma (DLBCL) without a history of CLL were absent. These results suggest that clonally unrelated RS is a truly de novo lymphoma with a mutational profile reminiscent, at least in part, of clonally related RS.<\/jats:p>","DOI":"10.1111\/bjh.18352","type":"journal-article","created":{"date-parts":[[2022,7,13]],"date-time":"2022-07-13T14:18:32Z","timestamp":1657721912000},"page":"1016-1022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Clonally unrelated Richter syndrome are truly de novo diffuse large B\u2010cell lymphomas with a mutational profile reminiscent of clonally related Richter syndrome"],"prefix":"10.1111","volume":"198","author":[{"given":"Chiara","family":"Favini","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Translational Medicine Universit\u00e0 del Piemonte Orientale  Novara 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