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    Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.

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    Authors
    Gale, K B
    Ford, A M
    Repp, R
    Borkhardt, A
    Keller, C
    Eden, Tim O B
    Greaves, M F
    Affiliation
    Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
    Issue Date
    1997-12-09
    
    Metadata
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    Abstract
    Epidemiological evidence has suggested that some pediatric leukemias may be initiated in utero and, for some pairs of identical twins with concordant leukemia, this possibility has been strongly endorsed by molecular studies of clonality. Direct evidence for a prenatal origin can only be derived by prospective or retrospective detection of leukemia-specific molecular abnormalities in fetal or newborn samples. We report a PCR-based method that has been developed to scrutinize neonatal blood spots (Guthrie cards) for the presence of numerically infrequent leukemic cells at birth in individuals who subsequently developed leukemia. We demonstrate that unique or clonotypic MLL-AF4 genomic fusion sequences are present and detectable in neonatal blood spots from individuals who were diagnosed with acute lymphoblastic leukemia at ages 5 months to 2 years and, therefore, have arisen during fetal hematopoiesis in utero. This result provides unequivocal evidence for a prenatal initiation of acute leukemia in young patients. The method should be applicable to other fusion genes in children with common subtypes of leukemia and will be of value in attempts to unravel the natural history and etiology of this major subtype of pediatric cancer.
    Citation
    Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots. 1997, 94 (25):13950-4 Proc. Natl. Acad. Sci. U.S.A.
    Journal
    Proceedings of the National Academy of Sciences of the United States of America
    URI
    http://hdl.handle.net/10541/94685
    PubMed ID
    9391133
    Type
    Article
    Language
    en
    ISSN
    0027-8424
    Collections
    All Christie Publications

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