Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.
AffiliationLeukaemia Research Fund Centre at the Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
MetadataShow full item record
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.
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.
JournalProceedings of the National Academy of Sciences of the United States of America
- Detection of clonotypic IGH and TCR rearrangements in the neonatal blood spots of infants and children with B-cell precursor acute lymphoblastic leukemia.
- Authors: Yagi T, Hibi S, Tabata Y, Kuriyama K, Teramura T, Hashida T, Shimizu Y, Takimoto T, Todo S, Sawada T, Imashuku S
- Issue date: 2000 Jul 1
- Prenatal origin of childhood AML occurs less frequently than in childhood ALL.
- Authors: Burjanivova T, Madzo J, Muzikova K, Meyer C, Schneider B, Votava F, Marschalek R, Stary J, Trka J, Zuna J
- Issue date: 2006 Apr 21
- Identification of complex genomic breakpoint junctions in the t(9;11) MLL-AF9 fusion gene in acute leukemia.
- Authors: Super HG, Strissel PL, Sobulo OM, Burian D, Reshmi SC, Roe B, Zeleznik-Le NJ, Diaz MO, Rowley JD
- Issue date: 1997 Oct
- Fusion of an AF4-related gene, LAF4, to MLL in childhood acute lymphoblastic leukemia with t(2;11)(q11;q23).
- Authors: Hiwatari M, Taki T, Taketani T, Taniwaki M, Sugita K, Okuya M, Eguchi M, Ida K, Hayashi Y
- Issue date: 2003 May 8
- AF5q31, a newly identified AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23).
- Authors: Taki T, Kano H, Taniwaki M, Sako M, Yanagisawa M, Hayashi Y
- Issue date: 1999 Dec 7