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Blood, 15 July 2001, Vol. 98, No. 2, pp. 478-482
BRIEF REPORT
Molecular tracking of leukemogenesis in a triplet
pregnancy
Ana Teresa Maia,
Anthony M. Ford,
G. Reza Jalali,
Christine J. Harrison,
G.
Malcolm Taylor,
Osborn B. Eden, and
Mel F. Greaves
From the Leukaemia Research Fund Centre, Institute of
Cancer Research, Chester Beatty Laboratories, London; the Cytogenetics
Laboratory, Department of Haematology, Royal Free Hospital, London; the
Immunogenetics Laboratory, St Mary's Hospital, Manchester; and the
Academic Unit of Paediatric Oncology, Christie Hospital and Royal
Manchester Children's NHS Trusts, United Kingdom.
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.
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