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Myelodysplasias

T-cell receptor Vβ CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia

Leukemia volume 22, pages 1170–1174 (2008)Cite this article

Abstract

(Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure syndrome characterized by immune-mediated destruction of hematopoietic progenitors. MDS is a malignant clonal stem cell disorder, of which the hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to separate from (v)SAA. Recently, studies provided a molecular signature of autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of the TCR Vβ CDR3 region. We investigated retrospectively the frequency and the discriminative value of TCR Vβ CDR3 oligoclonality in pediatric (v)SAA and MDS patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls were analysed via TCR Vβ heteroduplex PCR analysis of extracted RNA. A skewed TCR Vβ CDR3 repertoire was found in 21/38 (v)SAA and in 17/28 RC patients in contrast to 2/18 in the control group. These data suggest an overlapping group of RC and SAA patients that may share a common immune-mediated pathogenesis. Prospective studies are required to establish the clinical value of TCR Vβ CDR3 repertoire analysis to predict the clinical response in these patients.

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Acknowledgements

We thank E Velleuer for collecting a subset of the data for this study. This project was supported by a grant from the Foundation KiKa, Amstelveen, The Netherlands.

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Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands

    A C H de Vries, C M Zwaan, A Beishuizen, R Pieters & M M van den Heuvel-Eibrink

  2. Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands

    A W Langerak & B Verhaaf

  3. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany

    C M Niemeyer

  4. Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School, Prague, Czech Republic

    J Stary

  5. Rigshopitalet and University Hospital of Copenhagen, Copenhagen, Denmark

    K Schmiegelow

  6. Dutch Childhood Oncology Group, The Hague, The Netherlands

    E R van Wering, C M Zwaan & M M van den Heuvel-Eibrink

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  1. A C H de Vries
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  2. A W Langerak
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Correspondence to M M van den Heuvel-Eibrink.

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de Vries, A., Langerak, A., Verhaaf, B. et al. T-cell receptor Vβ CDR3 oligoclonality frequently occurs in childhood refractory cytopenia (MDS-RC) and severe aplastic anemia. Leukemia 22, 1170–1174 (2008). https://doi.org/10.1038/leu.2008.23

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