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However, in the unfavorable subset 2, an acquired mutation (termed R110) in the light chain stimulates autonomous BCR signaling. This study demonstrates that the oncogenic R110 mutation dictates the unfavorable prognosis and is not restricted to the conventional subset 2. Interestingly, carriers of a particular light-chain allele (\n                    <jats:italic>\n                      IGLV3-21\n                      <jats:italic>*<\/jats:italic>\n                      01\n                    <\/jats:italic>\n                    ) are predisposed to develop CLL because this allele enables autonomous BCR signaling by R110 as a single-point mutation. Monoclonal antibodies permit convenient screening for R110-expressing CLL, showing that it is the largest immunologically defined CLL subset and an example of functional rather than empirical CLL subclassification.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1913810117","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T16:55:37Z","timestamp":1581440137000},"page":"4320-4327","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["<i>\n                      IGLV3-21\n                      <i>*<\/i>\n                      01\n                    <\/i>\n                    is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling"],"prefix":"10.1073","volume":"117","author":[{"given":"Palash C.","family":"Maity","sequence":"first","affiliation":[{"name":"Institute of Immunology, Ulm University, 89081 Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayas","family":"Bilal","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Ulm University, 89081 Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvyn T.","family":"Koning","sequence":"additional","affiliation":[{"name":"Department of Hematology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Young","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Ulm University, 89081 Ulm, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-4517","authenticated-orcid":false,"given":"Cornelis A. 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