2.50
Hdl Handle:
http://hdl.handle.net/10541/84072
Title:
Molecular tracking of leukemogenesis in a triplet pregnancy.
Authors:
Maia, Ana Teresa; Ford, A M; Jalali, G Reza; Harrison, Christine J; Taylor, G Malcolm; Eden, Tim O B; Greaves, Mel F
Abstract:
The 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.
Affiliation:
Leukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.
Citation:
Molecular tracking of leukemogenesis in a triplet pregnancy. 2001, 98 (2):478-82 Blood
Journal:
Blood
Issue Date:
15-Jul-2001
URI:
http://hdl.handle.net/10541/84072
PubMed ID:
11435320
Type:
Article
Language:
en
ISSN:
0006-4971
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMaia, Ana Teresaen
dc.contributor.authorFord, A Men
dc.contributor.authorJalali, G Rezaen
dc.contributor.authorHarrison, Christine Jen
dc.contributor.authorTaylor, G Malcolmen
dc.contributor.authorEden, Tim O Ben
dc.contributor.authorGreaves, Mel Fen
dc.date.accessioned2009-10-12T15:54:57Z-
dc.date.available2009-10-12T15:54:57Z-
dc.date.issued2001-07-15-
dc.identifier.citationMolecular tracking of leukemogenesis in a triplet pregnancy. 2001, 98 (2):478-82 Blooden
dc.identifier.issn0006-4971-
dc.identifier.pmid11435320-
dc.identifier.urihttp://hdl.handle.net/10541/84072-
dc.description.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.en
dc.language.isoenen
dc.subjectCancer DNAen
dc.subjectPrecursor Cell Lymphoblastic Leukaemia-Lymphomaen
dc.subject.meshBase Sequence-
dc.subject.meshCore Binding Factor Alpha 2 Subunit-
dc.subject.meshDNA, Neoplasm-
dc.subject.meshDiseases in Twins-
dc.subject.meshFemale-
dc.subject.meshGene Deletion-
dc.subject.meshHumans-
dc.subject.meshIn Situ Hybridization, Fluorescence-
dc.subject.meshInfant-
dc.subject.meshMale-
dc.subject.meshMicrosatellite Repeats-
dc.subject.meshOncogene Proteins, Fusion-
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphoma-
dc.subject.meshPregnancy-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshTranslocation, Genetic-
dc.subject.meshTriplets-
dc.subject.meshTwins, Dizygotic-
dc.subject.meshTwins, Monozygotic-
dc.titleMolecular tracking of leukemogenesis in a triplet pregnancy.en
dc.typeArticleen
dc.contributor.departmentLeukaemia Research Fund Centre, Institute of Cancer Research, Chester Beatty Laboratories, London, United Kingdom.en
dc.identifier.journalBlooden

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