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Cytogenetics and Molecular Genetics

A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia

Leukemia volume 20, pages 1245–1253 (2006)Cite this article

Abstract

Over the last decade, genetic characterization of T-cell acute lymphoblastic leukemia (T-ALL) has led to the identification of a variety of chromosomal abnormalities. In this study, we used array-comparative genome hybridization (array-CGH) and identified a novel recurrent 9q34 amplification in 33% (12/36) of pediatric T-ALL samples, which is therefore one of the most frequent cytogenetic abnormalities observed in T-ALL thus far. The exact size of the amplified region differed among patients, but the critical region encloses ∼4 Mb and includes NOTCH1. The 9q34 amplification may lead to elevated expression of various genes, and MRLP41, SSNA1 and PHPT1 were found significantly expressed at higher levels. Fluorescence in situ hybridization (FISH) analysis revealed that this 9q34 amplification was in fact a 9q34 duplication on one chromosome and could be identified in 17–39 percent of leukemic cells at diagnosis. Although this leukemic subclone did not predict for poor outcome, leukemic cells carrying this duplication were still present at relapse, indicating that these cells survived chemotherapeutic treatment. Episomal NUP214-ABL1 amplification and activating mutations in NOTCH1, two other recently identified 9q34 abnormalities in T-ALL, were also detected in our patient cohort. We showed that both of these genetic abnormalities occur independently from this newly identified 9q34 duplication.

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Acknowledgements

Research Support: P.V.V. is financed by a grant from the Sophia Foundation for Medical Research (SSWO Grant 440). This study was supported by Ter Meulen Fund, Royal Netherlands Academy of Arts and Sciences, and the Foundation ‘De Drie Lichten’.

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Author notes

  1. J C Aster and R Pieters: These authors can be regarded as co-last authors

Authors and Affiliations

  1. Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands

    P van Vlierberghe, J P P Meijerink & R Pieters

  2. Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    C Lee & J C Aster

  3. Department of Pediatric Oncology, and Division of Hematology/Oncology, Dana-Farber Cancer Institute, Children's Hospital, Harvard Medical School, Boston, MA, USA

    A A Ferrando & A T Look

  4. Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands

    E R van Wering

  5. Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands

    H B Beverloo

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  1. P van Vlierberghe
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Correspondence to J P P Meijerink.

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van Vlierberghe, P., Meijerink, J., Lee, C. et al. A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia. Leukemia 20, 1245–1253 (2006). https://doi.org/10.1038/sj.leu.2404247

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