AuthorsMaia, Ana Teresa
Ford, A M
Jalali, G Reza
Harrison, Christine J
Taylor, G Malcolm
Eden, Tim O B
Greaves, Mel F
AffiliationLeukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
MetadataShow full item record
AbstractThe occurrence of childhood acute lymphoblastic leukemia (ALL) in 2 of 3 triplets provided a unique opportunity for the investigation of leukemogenesis and the natural history of ALL. The 2 leukemic triplets were monozygotic twins and shared an identical, acquired TEL-AML1 genomic fusion sequence indicative of a single-cell origin in utero in one fetus followed by dissemination of clonal progeny to the comonozygotic twin by intraplacental transfer. In accord with this interpretation, clonotypic TEL-AML1 fusion sequences could be amplified from the archived neonatal blood spots of the leukemic twins. The blood spot of the third, healthy, dizygotic triplet was also fusion gene positive in a single segment, though at age 3 years, his blood was found negative by sensitive polymerase chain reaction (PCR) screening for the genomic sequence and by reverse transcription-PCR. Leukemic cells in both twins had, in addition to TEL-AML1 fusion, a deletion of the normal, nonrearranged TEL allele. However, this genetic change was found by fluorescence in situ hybridization to be subclonal in both twins. Furthermore, mapping of the genomic boundaries of TEL deletions using microsatellite markers indicated that they were individually distinct in the twins and therefore must have arisen as independent and secondary events, probably after birth. These data support a multihit temporal model for the pathogenesis of the common form of childhood leukemia.
CitationMolecular tracking of leukemogenesis in a triplet pregnancy. 2001, 98 (2):478-82 Blood
- Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.
- Authors: Ford AM, Bennett CA, Price CM, Bruin MC, Van Wering ER, Greaves M
- Issue date: 1998 Apr 14
- Prenatal origin of separate evolution of leukemia in identical twins.
- Authors: Teuffel O, Betts DR, Dettling M, Schaub R, Schäfer BW, Niggli FK
- Issue date: 2004 Oct
- Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero.
- Authors: Wiemels JL, Ford AM, Van Wering ER, Postma A, Greaves M
- Issue date: 1999 Aug 1
- Prenatal origin of acute lymphoblastic leukaemia in children.
- Authors: Wiemels JL, Cazzaniga G, Daniotti M, Eden OB, Addison GM, Masera G, Saha V, Biondi A, Greaves MF
- Issue date: 1999 Oct 30
- Origins of "late" relapse in childhood acute lymphoblastic leukemia with TEL-AML1 fusion genes.
- Authors: Ford AM, Fasching K, Panzer-Grümayer ER, Koenig M, Haas OA, Greaves MF
- Issue date: 2001 Aug 1