{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:26:38Z","timestamp":1780392398175,"version":"3.54.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T00:00:00Z","timestamp":1675728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate clinicopathologic characteristics of biclonal chronic lymphocytic leukemia (CLL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospectively analyze clinical data and pathologic features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten cases were identified in which flow cytometry demonstrated an abnormal B-cell population with a CLL-like immunophenotype but showed no definitive light chain restriction. All had cytogenetic abnormalities detected, including seven with two CLL-related abnormalities. Four of these showed features suggestive of clonal evolution, all having del(13q) as a \u201cstem-line\u201d abnormality and three showing del(11q) as a \u201cside-line\u201d abnormality. Five (50%) cases demonstrated deleterious NOTCH1 mutations, in contrast to 11.8% in a control group of monoclonal CLL (P\u2005&amp;lt;\u2005.05). Of the 10 patients, 5 received treatment, with good\/partial response in three cases and therapeutic resistance in one case. The median treatment-free survival was estimated at 68 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite a polytypic pattern of light chain expression, the neoplastic nature of biclonal CLL is suggested by a characteristic CLL phenotype and can be confirmed by cytogenetic and genomic analyses. The two clones with discordant light chain isotypes may share a \u201cstem-line\u201d cytogenetic abnormality, suggesting possible clonal evolution. Biclonal CLL is associated with NOTCH1 mutations, which may occur in a small subclone and gradually evolve in clonal size. Genomic analysis on light chain\u2013sorted and\/or chronologically collected samples may provide insight into clonal evolution in CLL.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ajcp\/aqac165","type":"journal-article","created":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T20:04:17Z","timestamp":1675800257000},"page":"337-351","source":"Crossref","is-referenced-by-count":7,"title":["Chronic Lymphocytic Leukemia With Two B-Cell Populations of Discordant Light Chain Restrictions in Individual Patients: Parallel Development of Biclonal B-Cell Neoplasms or Clonal Evolution With Isotype Switch?"],"prefix":"10.1093","volume":"159","author":[{"given":"Yue","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang , China"},{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imran","family":"Siddiqi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J","family":"Wildes","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"McCracken","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Deak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Rehder","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-6336","authenticated-orcid":false,"given":"Endi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Duke University School of Medicine , Durham, NC , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,7]]},"reference":[{"key":"2023040406403857100_","first-page":"216","article-title":"Chronic lymphocytic leukaemia\/small lymphocytic lymphoma.","volume-title":"WHO Classification of Tumours of Haematopoietic and Lymphoid 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