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

2.50
Hdl Handle:
http://hdl.handle.net/10541/94685
Title:
Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.
Authors:
Gale, K B; Ford, A M; Repp, R; Borkhardt, A; Keller, C; Eden, Tim O B; Greaves, M F
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.
Affiliation:
Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
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
Issue Date:
9-Dec-1997
URI:
http://hdl.handle.net/10541/94685
PubMed ID:
9391133
Type:
Article
Language:
en
ISSN:
0027-8424
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGale, K Ben
dc.contributor.authorFord, A Men
dc.contributor.authorRepp, Ren
dc.contributor.authorBorkhardt, Aen
dc.contributor.authorKeller, Cen
dc.contributor.authorEden, Tim O Ben
dc.contributor.authorGreaves, M Fen
dc.date.accessioned2010-03-23T14:46:31Z-
dc.date.available2010-03-23T14:46:31Z-
dc.date.issued1997-12-09-
dc.identifier.citationBacktracking 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.en
dc.identifier.issn0027-8424-
dc.identifier.pmid9391133-
dc.identifier.urihttp://hdl.handle.net/10541/94685-
dc.description.abstractEpidemiological 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.en
dc.language.isoenen
dc.subjectCancer DNAen
dc.subjectMyeloid-Lymphoid Leukaemia Proteinen
dc.subjectPrecursor Cell Lymphoblastic Leukaemia-Lymphomaen
dc.subject.meshArtificial Gene Fusion-
dc.subject.meshBase Sequence-
dc.subject.meshChild, Preschool-
dc.subject.meshDNA Primers-
dc.subject.meshDNA, Neoplasm-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFetal Blood-
dc.subject.meshHumans-
dc.subject.meshInfant-
dc.subject.meshInfant, Newborn-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshMyeloid-Lymphoid Leukemia Protein-
dc.subject.meshNuclear Proteins-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshProto-Oncogenes-
dc.subject.meshRetrospective Studies-
dc.subject.meshTranscription Factors-
dc.titleBacktracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.en
dc.typeArticleen
dc.contributor.departmentLeukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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