1. ¹Department of Pediatric Oncology/Hematology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands
2. ²Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands
3. ³Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany
4. ⁴Department of Pediatric Hematology and Oncology, Charles University, 2nd Medical School, Prague, Czech-Republic
5. ⁵Rigshopitalet and University Hospital of Copenhagen, Copenhagen, Denmark
6. ⁶Dutch Childhood Oncology Group, The Hague, The Netherlands

Correspondence: Dr MM van den Heuvel-Eibrink, Department of Pediatric Oncology and Hematology, Erasmus MC-Sophia Children's Hospital, Room Sp 2568, Dr Molewaterplein 60, Rotterdam 3015 GJ, The Netherlands. E-mail: m.vandenheuvel@erasmusmc.nl

Received 11 August 2007; Revised 20 January 2008; Accepted 23 January 2008; Published online 6 March 2008.

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 V CDR3 region. We investigated retrospectively the frequency and the discriminative value of TCR V 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 V heteroduplex PCR analysis of extracted RNA. A skewed TCR V 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 V CDR3 repertoire analysis to predict the clinical response in these patients.