[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
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:

Immunophenotype-defined sub-populations are common at diagnosis in childhood B-cell precursor acute lymphoblastic leukemia

Leukemia volume 25, pages 1652–1657 (2011)Cite this article

Subjects

Access through your institution
Buy or subscribe

Neoplasms often display significant heterogeneity in morphology, gene expression (including cell surface markers), genetic aberrations, cell proliferation kinetics and response to therapy.1 Heterogeneity in antigen marker expression is well known in acute myeloid leukemia (AML);2 however, has rarely been studied in acute lymphoblastic leukemia (ALL). In ALL, shifts in immunophenotypic and genetic profiles can occur between diagnosis and relapse.3 Such changes of immune gene-rearrangement profiles can reflect the presence at diagnosis of minor, but genomically distinct sub-populations.4 Likewise, changes in immunophenotype might reflect phenotypically distinct sub-populations at diagnosis that potentially could be detected in a more sensitive flow-cytometric analysis than used routinely. If such sub-populations are present and different immunophenotypes are related to differences in gene rearrangement profiles, this could cause discordances between the methods for minimal residual disease (MRD) monitoring, that is, flow-cytometric immunophenotyping and PCR-based detection of clonotypic immunoglobulin (Ig)/T-cell receptor (TCR) gene rearrangements. Importantly, sub-populations are also relevant for the understanding of the ontogenesis of the malignant cells and might give clues for understanding the biological mechanisms of therapy resistance and relapse.

In this study, we explored the presence at diagnosis of immunophenotypically heterogeneous leukemic cell populations, that is, distinct sub-populations with bimodal marker expression or populations with broad marker expression, in childhood B-cell precursor (BCP) ALL. Immunophenotypically heterogeneous cells were isolated by flow sorting and investigated for the clone-defining cytogenetic marker and a broad spectrum of clonal Ig/TCR gene rearrangements.

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2

References

  1. Marusyk A, Polyak K . Tumor heterogeneity: causes and consequences. Biochim Biophys Acta 2010; 1805: 105–107.

    CAS  PubMed  Google Scholar 

  2. Al-Mawali A, Gillis D, Lewis I . The role of multiparameter flow cytometry for detection of minimal residual disease (MRD) in acute myeloid leukemia (AML). Am J Clin Pathol 2009; 131: 16–26.

    Article  Google Scholar 

  3. Borowitz MJ, Pullen DJ, Winick N, Martin PL, Bowman WP, Camitta B . Comparison of diagnostic and relapse flow cytometry phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a report from the children's oncology group. Cytometry B Clin Cytom 2005; 68: 18–24.

    Article  Google Scholar 

  4. Choi S, Hendersen MJ, Ewans E, Beesley AH, Sutton R, Bahar AY et al. Relapse in children with acute lymphoblastic leukemia involving selection of a pre-existing drug-resistant subclone. Blood 2007; 110: 632–639.

    Article  CAS  Google Scholar 

  5. Obro NF, Madsen HO, Ryder LP, Andersen MK, Schmiegelow K, Marquart HV . Approaches for cytogenetic and molecular analyses of small flow-sorted cell populations from childhood leukemia bone marrow samples. J Immunol Methods 2011; e-pub ahead of print 6 May 2011.

  6. Stahnke K, Eckhoff S, Mohr A, Meyer LH, Debatin KM . Apoptosis induction in peripheral leukemia cells by remission induction treatment in vivo: selective depletion and apoptosis in a CD34+ subpopulation of leukemia cells. Leukemia 2003; 17: 2130–2139.

    Article  CAS  Google Scholar 

  7. Lucio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E et al. Flow cytometric analysis of normal B cell differentiation: a fram of reference for the detection of minimal residual disease in precursor B-ALL. Leukemia 1999; 13: 419–427.

    Article  CAS  Google Scholar 

  8. Dick JE . Stem cell concepts renew cancer research. Blood 2008; 112: 4793–4807.

    Article  CAS  Google Scholar 

  9. Dworzak MN, Gaipa G, Schumich A, Maglia O, Ratei R, Veltroni M et al. Modulation of antigen expression in B-cell precursor acute lymphoblastic leukemia during induction therapy is partly transient: evidence for a drug-induced regulatory phenomenon. Results of the AIEOP-BFM-ALL-FLOW-MRD-Study Group. Cytometry B Clin Cytom 2010; 78: 147–153.

    Google Scholar 

Download references

Acknowledgements

This study has received financial support from the Ministry of Health (Grant number 2006-12103-250), the Novo Nordic Foundation, the Danish Research Council for Health and Disease (Grant number R20-A1156-10-S2), the Danish Childhood Cancer Foundation (Grant no. 2008/2) and the Otto Christensen Foundation. Kjeld Schmiegelow holds the Danish Childhood Cancer Foundation Professorship in Pediatric Oncology.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology, University Hospital Rigshospitalet, Copenhagen, Denmark

    N F Øbro, H V Marquart, H O Madsen & L P Ryder

  2. Department of Clinical Genetics, University Hospital Rigshospitalet, Copenhagen, Denmark

    M K Andersen

  3. Department of Pediatrics, University Hospital Rigshospitalet, Copenhagen, Denmark

    B Lausen & K Schmiegelow

  4. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark

    B K Albertsen

  5. Department of Pediatric Hematology and Oncology, H. C. Andersen Children′s Hospital, Odense University Hospital, Odense, Denmark

    P S Wehner

  6. Department of Pediatrics, Aarhus University Hospital Aalborg, Aalborg, Denmark

    J Helgestad

  7. The Institute of Gynecology, Obstetrics and Pediatrics, The Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

Authors
  1. N F Øbro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H V Marquart
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H O Madsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L P Ryder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M K Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Lausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B K Albertsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P S Wehner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Helgestad
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K Schmiegelow
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H V Marquart.

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

Øbro, N., Marquart, H., Madsen, H. et al. Immunophenotype-defined sub-populations are common at diagnosis in childhood B-cell precursor acute lymphoblastic leukemia. Leukemia 25, 1652–1657 (2011). https://doi.org/10.1038/leu.2011.136

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.136

Search

Advanced search

Quick links