Monoclonal B lymphocytes with the characteristics of “indolent” chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts

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 undetermin...

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Bibliographic Details
Published in:	Blood Vol. 100; no. 2; pp. 635 - 639
Main Authors:	Rawstron, Andy C., Green, Michael J., Kuzmicki, Anita, Kennedy, Ben, Fenton, James A.L., Evans, Paul A.S., O'Connor, Sheila J.M., Richards, Stephen J., Morgan, Gareth J., Jack, Andrew S., Hillmen, Peter
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 15-07-2002 The Americain Society of Hematology
Subjects:	Adult Age Factors Aged Aged, 80 and over B-Lymphocytes - pathology Biological and medical sciences Blood Cell Count Cell Transformation, Neoplastic - pathology Clone Cells - pathology Female Flow Cytometry Genes, Immunoglobulin Hematologic and hematopoietic diseases Humans Immunophenotyping Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis Leukemia, Lymphocytic, Chronic, B-Cell - epidemiology Leukemia, Lymphocytic, Chronic, B-Cell - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Mass Screening - methods Medical sciences Middle Aged Prevalence Sex Factors Human Genetic marker Biological marker Early stage Malignant hemopathy Asymptomatic B-Lymphocyte Molecular marker Medical screening Chronic Chronic lymphocytic leukemia Phenotype Cell population Lymphoproliferative syndrome Low malignancy
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Summary:	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 × 109 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 = .01). The neoplastic cells were identical to good-prognosis CLL, being CD5+23+20wk79bwk11a−22wksIgwkCD38−, 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.
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood.V100.2.635