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Blood, 15 July 2002, Vol. 100, No. 2, pp. 635-639
NEOPLASIA
Monoclonal B lymphocytes with the characteristics of
"indolent" chronic lymphocytic leukemia are present in 3.5% of
adults with normal blood counts
Andy C. Rawstron,
Michael
J. Green,
Anita Kuzmicki,
Ben Kennedy,
James A. L. Fenton,
Paul A. S. Evans,
Sheila J. M. O'Connor,
Stephen J. Richards,
Gareth J. Morgan,
Andrew S. Jack, and
Peter Hillmen
From Haematological Malignancy Diagnostic Service,
Academic Unit of Haematology and Oncology, Algernon Firth Building,
University of Leeds, United Kingdom.
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.

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