{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:15:10Z","timestamp":1790158510420,"version":"4.1.0"},"reference-count":34,"publisher":"American Society of Hematology","issue":"2","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Molecular and cellular markers associated with malignant disease are frequently identified in healthy individuals. The relationship between these markers and clinical disease is not clear, except where a neoplastic cell population can be identified as in myeloma\/monoclonal gammopathies of undetermined significance (MGUS). We have used the distinctive phenotype of chronic lymphocytic leukemia (CLL) cells to determine whether low levels of these cells can be identified in individuals with normal complete blood counts. CLL cells were identified by 4-color flow cytometric analysis of CD19\/CD5\/CD79b\/CD20 expression in 910 outpatients over 40 years old. These outpatients were age- and sex-matched to the general population with normal hematologic parameters and no evident history of malignant disease. CLL phenotype cells were detectable in 3.5% of individuals at low level (median, 0.013; range, 0.002- 1.458\u2009\u00d7\u2009109 cells\/L), and represented a minority of B lymphocytes (median, 11%; range, 3%-95%). Monoclonality was demonstrated by immunoglobulin light-chain restriction in all cases with CLL phenotype cells present and confirmed in a subset of cases by consensus-primer IgH-polymerase chain reaction. As in clinical disease, CLL phenotype cells were detected with a higher frequency in men (male-to-female ratio, 1.9:1) and elderly individuals (2.1% of 40- to 59-year-olds versus 5.0% of 60- to 89-year-olds, P\u2009=\u2009.01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20wk79bwk11a\u221222wksIgwkCD38\u2212, and where assessed had a high degree (4.8%-6.6%) of IgH somatic hypermutation. The monoclonal CLL phenotype cells present in otherwise healthy individuals may represent a very early stage of indolent CLL and should be useful in elucidating the mechanisms of leukemogenesis.<\/jats:p>","DOI":"10.1182\/blood.v100.2.635","type":"journal-article","created":{"date-parts":[[2002,10,1]],"date-time":"2002-10-01T17:48:18Z","timestamp":1033494498000},"page":"635-639","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":271,"title":["Monoclonal B lymphocytes with the characteristics of \u201cindolent\u201d chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts"],"prefix":"10.1182","volume":"100","author":[{"given":"Andy C.","family":"Rawstron","sequence":"first","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Green","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Kuzmicki","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Kennedy","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A. L.","family":"Fenton","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A. S.","family":"Evans","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila J. M.","family":"O'Connor","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Richards","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth J.","family":"Morgan","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew S.","family":"Jack","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hillmen","sequence":"additional","affiliation":[{"name":"From Haematological Malignancy Diagnostic Service, Academic Unit of Haematology and Oncology, Algernon Firth Building, University of Leeds, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021219274434900_B1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1056\/NEJM199104253241702","article-title":"Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.","volume":"324","author":"Catalona","year":"1991","journal-title":"N Engl J Med."},{"key":"2020021219274434900_B2","doi-asserted-by":"crossref","first-page":"8910","DOI":"10.1073\/pnas.91.19.8910","article-title":"BCL2 translocation frequency rises with age in humans.","volume":"1","author":"Liu","year":"1994","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2020021219274434900_B3","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1182\/blood.V85.9.2528.bloodjournal8592528","article-title":"Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals.","volume":"85","author":"Limpens","year":"1995","journal-title":"Blood."},{"key":"2020021219274434900_B4","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1200\/JCO.1996.14.4.1333","article-title":"BCL-2\/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases.","volume":"14","author":"Dolken","year":"1996","journal-title":"J Clin Oncol."},{"key":"2020021219274434900_B5","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1182\/blood.V92.9.3362","article-title":"The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: biologic significance and implications for the assessment of minimal residual disease.","volume":"92","author":"Bose","year":"1998","journal-title":"Blood."},{"key":"2020021219274434900_B6","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1182\/blood.V86.8.3118.3118","article-title":"Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals.","volume":"86","author":"Biernaux","year":"1995","journal-title":"Blood."},{"key":"2020021219274434900_B7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1182\/blood.V88.1.289.289","article-title":"Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma.","volume":"88","author":"Billadeau","year":"1996","journal-title":"Blood."},{"key":"2020021219274434900_B8","doi-asserted-by":"crossref","first-page":"2658","DOI":"10.1182\/blood.V81.10.2658.2658","article-title":"Phenotypic difference of normal plasma cells from mature myeloma cells.","volume":"81","author":"Harada","year":"1993","journal-title":"Blood."},{"key":"2020021219274434900_B9","first-page":"1655","article-title":"Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. 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Intergroupe Francophone du Myelome.","volume":"59","author":"Avet-Loiseau","year":"1999","journal-title":"Cancer Res."},{"key":"2020021219274434900_B14","first-page":"283","article-title":"IgH translocations in multiple myeloma: a nearly universal event that rarely involves c-myc.","volume":"224","author":"Bergsagel","year":"1997","journal-title":"Curr Top Microbiol Immunol."},{"key":"2020021219274434900_B15","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1182\/blood.V96.12.3880","article-title":"The interleukin-6 receptor alpha-chain (CD126) is expressed by neoplastic but not normal plasma cells.","volume":"96","author":"Rawstron","year":"2000","journal-title":"Blood."},{"key":"2020021219274434900_B16","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1182\/blood.V94.8.2583.420a05_2583_2589","article-title":"Monosomy 13 is associated with the transition of monoclonal gammopathy of undetermined significance to multiple myeloma. 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