Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

CLL-like B-lymphocytes are systematically present at very low numbers in peripheral blood of healthy adults

Leukemia volume 25, pages 718–722 (2011)Cite this article

Subjects

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the Western world. The disease is typically diagnosed in adults >40 years old, who show an expansion (>5 × 109 cells per l) of clonal B-cells with a unique CD5+, CD23+, B-cell receptor (BCR)low immunophenotype in peripheral blood (PB) and bone marrow, frequently in association with involvement of other lymphoid tissues, disease symptoms and a heterogeneous clinical outcome. In parallel, monoclonal B-cell lymphocytosis (MBL), typically characterized by an expansion of clonal CLL-like B-cells (<5 × 109 cells per l), has been also frequently reported in otherwise asymptomatic subjects.1, 2 Increasing evidence suggests that this could represent a pre-leukemic condition, as CLL frequently develops in individuals with previous history of MBL, and MBL cases progress to CLL at a rate of 1% per year.2, 3

Interestingly, in addition to MBL cases presenting with lymphocytosis, very low numbers of clonal B-cells with a CLL-like immunophenotype and cytogenetic profile, are also present in healthy subjects with normal lymphocyte counts.2 Initially, a frequency of CLL-like clones among healthy adults of around 3–6% was reported. Despite this relatively high incidence, controversial results have been reported about the precise frequency of CLL-like MBL in the general population.2, 4, 5 Such variability has been related to genetic and microenvironmental differences, as well as to technical variables associated with different sensitivities of the distinct methods applied.4, 5 Accordingly, we have recently shown that the actual frequency of MBL cases presenting with normal lymphocyte counts could increase to as high as 12% of the general adult population >40 years,4 depending on the sensitivity of the method and the volume of blood screened, in addition to age. Altogether, these observations raise the question about the actual frequency and significance of such small B-cell clones in normal subjects, as regards their pathological vs physiological nature.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Marti GE, Rawstron AC, Ghia P, Hillmen P, Houlston RS, Kay N et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol 2005; 130: 325–332.

    Article  PubMed  Google Scholar 

  2. Shanafelt TD, Ghia P, Lanasa MC, Landgren O, Rawstron AC . Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management. Leukemia 2010; 24: 512–520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P et al. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 2009; 360: 659–667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nieto WG, Almeida J, Romero A, Teodosio C, Lopez A, Henriques AF et al. Increased frequency (12%) of circulating chronic lymphocytic leukemia-like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach. Blood 2009; 114: 33–37.

    Article  CAS  PubMed  Google Scholar 

  5. Shim YK, Middleton DC, Caporaso NE, Rachel JM, Landgren O, Abbasi F et al. Prevalence of monoclonal B-cell lymphocytosis: A systematic review. Cytometry B Clin Cytom 2010; 78 (Suppl 1): S10–S18.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Anderson LA, Landgren O, Engels EA . Common community acquired infections and subsequent risk of chronic lymphocytic leukaemia. Br J Haematol 2009; 147: 444–449.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Rawstron AC, Shanafelt T, Lanasa MC, Landgren O, Hanson C, Orfao A et al. Different biology and clinical outcome according to the absolute numbers of neoplastic B-cells in monoclonal B-cell lymphocytosis (MBL). Cytometry B Clin Cytom 2010; 78 (Suppl 1): S19–S23.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lanasa MC, Allgood SD, Volkheimer AD, Gockerman JP, Whitesides JF, Goodman BK et al. Single-cell analysis reveals oligoclonality among ‘low-count’ monoclonal B-cell lymphocytosis. Leukemia 2010; 24: 133–140.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work has been partially supported by the following grants: RTICC RD06/0020/0035-FEDER, PI06/0824 and PS09/02430 from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain; GRS206/A/08 from the Gerencia Regional de Salud de Castilla y León and Ayuda al Grupo GR37 de Excelencia de Castilla y León, Consejería de Educación, and SAN/1778/2009, Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain; FS/16-2008, from the Fundación Samuel Solórzano, University of Salamanca, Salamanca, Spain and Fundación Carolina, CNPq- Brazilian National Research Council, Brasília, Brazil and by a grant from FAPERJ—Río de Janeiro Research Foundation, Río de Janeiro, Brazil. AR-C is supported by Fundación Científica de la Asociación Española contra el Cáncer.

Author information

Authors and Affiliations

  1. Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer/IBMCC (CSIC-USAL), Salamanca, Spain

    J Almeida, W G Nieto, C Teodosio, A López, A Nieto, A Rodríguez-Caballero, M Jara-Acevedo & A Orfao

  2. Servicio de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain

    J Almeida, W G Nieto, C Teodosio, A López, A Nieto, A Rodríguez-Caballero & M Jara-Acevedo

  3. School of Medicine and COPPE-PEE-Engineering Graduate Program, Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil

    C E Pedreira

  4. Centro de Atención Primaria de Salud de Ledesma Salamanca, Sanidad de Castilla y León (SACYL), Castilla y León, Spain

    P Fernández-Navarro

  5. Servicio de Microbiología, Hospital Universitario de Salamanca, Salamanca, Spain

    S Muñoz-Criado

  6. Gerencia de Atención Primaria de Salud de Salamanca, Sanidad de Castilla y León (SACYL), Castilla y León, Spain

    A Romero

Authors
  1. J Almeida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W G Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Teodosio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C E Pedreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A López
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Fernández-Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Nieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Rodríguez-Caballero
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Muñoz-Criado
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Jara-Acevedo
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A Romero
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. A Orfao
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Primary Health Care Group of Salamanca for the Study of MBL

Corresponding author

Correspondence to A Orfao.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Almeida, J., Nieto, W., Teodosio, C. et al. CLL-like B-lymphocytes are systematically present at very low numbers in peripheral blood of healthy adults. Leukemia 25, 718–722 (2011). https://doi.org/10.1038/leu.2010.305

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2010.305

This article is cited by

Search

Advanced search

Quick links