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Prenatal origin of hyperdiploid acute lymphoblastic leukemia in identical twins

Leukemia volume 17, pages 2202–2206 (2003)Cite this article

Abstract

Studies in identical twins and with neonatal blood spots (Guthrie cards) have backtracked the origin of childhood acute leukemia and their associated chromosomal translocations to before birth. High hyperdiploidy is the most common genetic abnormality in childhood acute lymphoblastic leukemia (ALL). Evidence for an in utero initiation of this important genetic event in ALL is available from blood spots but remains limited. Twin children with hyperdiploid ALL have not hitherto been reported. We describe a pair of 2-year-old monozygotic twins with concordant B-cell precursor ALL and hyperdiploid karyotypes. One twin's leukemic cells had two rearranged TCRD alleles and one of these was a clonotypic Vδ2–Dδ3 sequence shared with leukemic cells of the other twin. The twins' leukemic cells had several different IGH VH–JH rearrangements but shared two common DH–JH ‘stem’ sequences. We conclude that ALL in these twins is likely to have originated prenatally in one fetus before spreading to the other via intraplacental anastomoses. It is likely that one or more additional postnatal genetic events was required for overt leukemogenesis.

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Acknowledgements

This work was supported by the Leukaemia Research Fund programme grants (CJH and MG), the Foundation for Science and Technology, Portugal (PRAXIS XXI/BD/19575/99) (ATM) and the Dutch Cancer Society/Koningin Wilhelmina Fonds (Grant SNWLK 2000-2268) (VHJV and JJMO).

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Authors and Affiliations

  1. Chester Beatty Laboratories, Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK

    A T Maia & M F Greaves

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

    V H J van der Velden, T Szczepanski & J J M van Dongen

  3. Cancer Sciences Division, Leukaemia Research Fund Cytogenetics Group, University of Southampton, Southampton, UK

    C J Harrison

  4. Birmingham Children's Hospital, Birmingham, UK

    M D Williams

  5. Birmingham Women's Hospital, Regional Genetics Laboratory, Birmingham, UK

    M J Griffiths

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  1. A T Maia
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Maia, A., van der Velden, V., Harrison, C. et al. Prenatal origin of hyperdiploid acute lymphoblastic leukemia in identical twins. Leukemia 17, 2202–2206 (2003). https://doi.org/10.1038/sj.leu.2403101

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