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Acute Leukemias

Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

Leukemia volume 26, pages 2079–2085 (2012)Cite this article

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Abstract

Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3–4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with <80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.

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Acknowledgements

We are grateful to Dr A Devys, P Herry (EFS Nantes) and I Mollet (EFS Lyon) for their technical support. This study has been supported by the Swiss National Science Foundation (Grant 320030_130483).

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Authors and Affiliations

  1. HLA Laboratory, EFS Rhône Alpes, Lyon, France

    V Dubois

  2. Service of Medicine Genetics, University Hospital Geneva, Geneva, Switzerland

    F Sloan-Béna & S Gimelli

  3. HLA Laboratory, EFS Pays de la Loire, Nantes, France

    A Cesbron & K Gagne

  4. Department of Laboratory Medicine, University Medical Center, University of Groningen, Groningen, The Netherlands

    B G Hepkema

  5. EA4271, EFS Pays de la Loire, Nantes, France

    K Gagne

  6. Division of Hematology, University Hospital Basel, Basel, Switzerland

    D Heim & A Tichelli

  7. Service of Clinical Hematology, CHU Hotel Dieu Nantes, Nantes, France

    J Delaunay

  8. Histocompatibility Laboratory, CHU Limoges, Limoges, France

    M Drouet

  9. National Reference Laboratory for Histocompatibility, Transplantation Immunology Unit, University Hospital Geneva, Geneva, Switzerland

    S Jendly, J Villard & J-M Tiercy

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  1. V Dubois
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  12. J Villard
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Correspondence to J-M Tiercy.

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Dubois, V., Sloan-Béna, F., Cesbron, A. et al. Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy. Leukemia 26, 2079–2085 (2012). https://doi.org/10.1038/leu.2012.68

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