{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:14:01Z","timestamp":1792725241642,"version":"4.5.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1997,12,9]]},"abstract":"<jats:p>\n                    Epidemiological evidence has suggested that some pediatric leukemias may be initiated\n                    <jats:italic>in utero<\/jats:italic>\n                    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\n                    <jats:italic>MLL-AF4<\/jats:italic>\n                    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\n                    <jats:italic>in utero<\/jats:italic>\n                    . 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.94.25.13950","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:39Z","timestamp":1027679499000},"page":"13950-13954","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":454,"title":["Backtracking leukemia to birth: Identification of clonotypic gene fusion sequences in neonatal blood\u2009spots"],"prefix":"10.1073","volume":"94","author":[{"given":"Karin B.","family":"Gale","sequence":"first","affiliation":[{"name":"Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom; Department of Paediatrics, Haematology and Oncology, University of Giessen, Feulgenstrasse 12, D-35385 Giessen, Germany; and Academic Unit of Paediatric Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M.","family":"Ford","sequence":"additional","affiliation":[{"name":"Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom; Department of Paediatrics, Haematology and Oncology, University of Giessen, Feulgenstrasse 12, D-35385 Giessen, Germany; and Academic Unit of Paediatric Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinald","family":"Repp","sequence":"additional","affiliation":[{"name":"Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom; Department 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Fulham Road, London SW3 6JB, United Kingdom; Department of Paediatrics, Haematology and Oncology, University of Giessen, Feulgenstrasse 12, D-35385 Giessen, Germany; and Academic Unit of Paediatric Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osborn B.","family":"Eden","sequence":"additional","affiliation":[{"name":"Leukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom; Department of Paediatrics, Haematology and Oncology, University of Giessen, Feulgenstrasse 12, D-35385 Giessen, Germany; and Academic Unit of Paediatric Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mel F.","family":"Greaves","sequence":"additional","affiliation":[{"name":"Leukaemia Research Fund Centre at the 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