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Chronic Lymphocytic Leukemia

Single-cell analysis reveals oligoclonality among ‘low-count’ monoclonal B-cell lymphocytosis

Leukemia volume 24, pages 133–140 (2010)Cite this article

Abstract

Monoclonal B-cell lymphocytosis (MBL) is a preclinical hematologic syndrome characterized by small accumulations of CD5+ B lymphocytes. Most MBL share phenotypic characteristics with chronic lymphocytic leukemia (CLL). Although some MBL progress to CLL, most MBL have apparently limited potential for progression to CLL, particularly those MBL with normal absolute B-cell counts (‘low-count’ MBL). Most CLL are monoclonal and it is not known whether MBL are monoclonal or oligoclonal; this is important because it is unclear whether MBL represent indolent CLL or represent a distinct premalignant precursor before the development of CLL. We used flow cytometry analysis and sorting to determine immunophenotypic characteristics, clonality and molecular features of MBL from familial CLL kindreds. Single-cell analysis indicated four of six low-count MBL consisted of two or more unrelated clones; the other two MBL were monoclonal. 87% of low-count MBL clones had mutated immunoglobulin genes, and no immunoglobulin heavy-chain rearrangements of VH family 1 were observed. Some MBL were diversified, clonally related populations with evidence of antigen drive. We conclude that although low-count MBL share many phenotypic characteristics with CLL, many MBL are oligoclonal. This supports a model for step-wise development of MBL into CLL.

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Acknowledgements

We thank Dr Andy Rawstron for his thoughtful review of this paper. We thank the study participants for their willingness to participate in this study, and the hematology-oncology physicians, nurses and physician assistants for their special help. Flow cytometry was performed in the Duke Human Vaccine Institute Flow Cytometry Core Facility that is supported by the National Institutes of Health award AI-51445.

Grant Support: MC Lanasa is a fellow of the Leukemia and Lymphoma Society of America. This research was funded by the Bernstein Fund for Leukemia Research, the VA Research Service and a grant from the National Institutes of Health (NCI R03 CA128030).

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Authors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    M C Lanasa, S D Allgood, A D Volkheimer, J P Gockerman, J O Moore & J B Weinberg

  2. Department of Medicine, Durham Veterans Affairs Medical Center, Durham, NC, USA

    A D Volkheimer & J B Weinberg

  3. Human Vaccine Institute, Duke University Medical Center, Durham, NC, USA

    J F Whitesides

  4. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    B K Goodman

  5. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    M C Levesque

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  1. M C Lanasa
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Correspondence to M C Lanasa.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Lanasa, M., Allgood, S., Volkheimer, A. et al. Single-cell analysis reveals oligoclonality among ‘low-count’ monoclonal B-cell lymphocytosis. Leukemia 24, 133–140 (2010). https://doi.org/10.1038/leu.2009.192

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