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Chronic Lymphocytic Leukemia

Immunophenotypic and gene expression analysis of monoclonal B-cell lymphocytosis shows biologic characteristics associated with good prognosis CLL

Leukemia volume 25, pages 1459–1466 (2011)Cite this article

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Abstract

Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and ‘CLL-like’ MBL is a precursor to CLL. We used flow cytometry to identify MBL from unaffected members of CLL kindreds. We identified 101 MBL cases from 622 study subjects; of these, 82 individuals with MBL were further characterized. In all, 91 unique MBL clones were detected: 73 CLL-like MBL (CD5+CD20dimsIgdim), 11 atypical MBL (CD5+CD20+sIg+) and 7 CD5neg MBL (CD5negCD20+sIgneg). Extended immunophenotypic characterization of these MBL subtypes was performed, and significant differences in cell surface expression of CD23, CD49d, CD79b and FMC-7 were observed among the groups. Markers of risk in CLL such as CD38, ZAP70 and CD49d were infrequently expressed in CLL-like MBL, but were expressed in the majority of atypical MBL. Interphase cytogenetics was performed in 35 MBL cases, and del 13q14 was most common (22/30 CLL-like MBL cases). Gene expression analysis using oligonucleotide arrays was performed on seven CLL-like MBL, and showed activation of B-cell receptor associated pathways. Our findings underscore the diversity of MBL subtypes and further clarify the relationship between MBL and other lymphoproliferative disorders.

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Acknowledgements

MC Lanasa is supported by the Duke Clinical Oncology Research Clinical Development Program (K12) and is a fellow of the Leukemia and Lymphoma Society of America. This research is supported by the Leukemia and Lymphoma Society of America, the Harold Bernstein Family Fund, the VA Research Service and grants from the National Institutes of Health (NCI R03 CA128030, NCI R01 CA95241 and NCI U01 CA118444). We thank the study research subjects for their willingness to participate in this study and the hematology–oncology 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.

Author contributions

All authors reviewed and approved the paper. Designed research: MCLa. Performed research: MCLa and SDA. Contributed vital analytical tools: SSD and BKG. Contributed Genetic Epidemiology of CLL samples and data: MCLa, SLS, GEM, NEK, NJC, CAH, LRG, VJC, CMV, LGS, LZR, JFL, SSS, TGC, JRC and MG. Collected data: MCLa and SDA. Analyzed and interpreted data: MCLa, SDA, SSD, MCLa, SLS, KGR, SJA and CL. Wrote the paper: MCLa, JBW and NEC.

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Authors and Affiliations

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

    M C Lanasa, S D Allgood, S S Dave, C Love, J P Gockerman & J B Weinberg

  2. Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA

    S L Slager, K G Rabe, S J Achenbach, C M Vachon & J R Cerhan

  3. Cellular and Tissue Therapy Branch, CBER, OCTGC, Food and Drug Administration, Rockville, MD, USA

    G E Marti

  4. Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA

    N E Kay & T G Call

  5. Department of Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA

    C A Hanson

  6. Genetic Epidemiology Branch, National Cancer Institute, Bethesda, MD, USA

    L R Goldin

  7. Department of Biomedical Informatics, University of Utah, Salt Lake City, UT, USA

    N J Camp

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

    B K Goodman

  9. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    L G Spector

  10. Department of Medicine, Moores UCSD Cancer Center, La Jolla, CA, USA

    L Z Rassenti & J B Weinberg

  11. Department of Medicine, Mayo Clinic College of Medicine, Scottsdale, AZ, USA

    J F Leis

  12. Department of Epidemiology, MD Anderson Cancer Center, Houston, TX, USA

    S S Strom

  13. Department of Medicine, University of Utah, Salt Lake City, UT, USA

    M Glenn

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

    M C Levesque

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

    N E Caporaso

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  1. M C Lanasa
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Correspondence to M C Lanasa.

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Lanasa, M., Allgood, S., Slager, S. et al. Immunophenotypic and gene expression analysis of monoclonal B-cell lymphocytosis shows biologic characteristics associated with good prognosis CLL. Leukemia 25, 1459–1466 (2011). https://doi.org/10.1038/leu.2011.117

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