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Prenatal origin of hyperdiploid acute lymphoblastic leukemia in identical twins

Lookup NU author(s): Professor Christine Harrison FRCPath FMedSci, Dr Michael Griffiths


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Studies in identical twins and with neonatal blood spots (Guthrie cards) have backtracked the origin of childhood acute leukemia and their associated chromosomal translocations to before birth. High hyperdiploidy is the most common genetic abnormality in childhood acute lymphoblastic leukemia (ALL). Evidence for an in utero initiation of this important genetic event in ALL is available from blood spots but remains limited. Twin children with hyperdiploid ALL have not hitherto been reported. We describe a pair of 2-year-old monozygotic twins with concordant B-cell precursor ALL and hyperdiploid karyotypes. One twin's leukemic cells had two rearranged TCRD alleles and one of these was a clonotypic Vdelta2-Ddelta3 sequence shared with leukemic cells of the other twin. The twins' leukemic cells had several different IGH V(H)-J(H) rearrangements but shared two common D(H)-J(H) 'stem' sequences. We conclude that ALL in these twins is likely to have originated prenatally in one fetus before spreading to the other via intraplacental anastomoses. It is likely that one or more additional postnatal genetic events was required for overt leukemogenesis.

Publication metadata

Author(s): Maia AT, van der Velden VH, Harrison CJ, Szczepanski T, Williams MD, Griffiths MJ, van Dongen JJ, Greaves MF

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2003

Volume: 17

Issue: 11

Pages: 2202-6

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

Publisher: Nature Publishing Group


DOI: 10.1038/sj.leu.2403101

Notes: Case Reports Journal Article Research Support, Non-U.S. Gov't England official journal of the Leukemia Society of America, Leukemia Research Fund, U.K


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