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Monoclonal origin of concordant T-cell malignancy in identical twins
AM Ford, MS Pombo-de-Oliveira, KP McCarthy, JM MacLean, KC Carrico, RF Vincent and M Greaves
Leukaemia Research Fund Centre, Institute for Cancer Research, London, UK.
Acute leukemia has a high concordance rate in young identical twins and in
infants this is known, from molecular analysis, to reflect an in utero
origin in one twin followed by prenatal metastasis to the other twin via
intraplacental anastomoses. The situation in older twins with leukemia has
been less clear. We describe a pair of identical twins who were diagnosed
with a T-cell malignancy at 9 and 11 years of age, one with T-cell
non-Hodgkin's lymphoma and the other with T-cell acute lymphoblastic
leukemia. Leukemic cells from the twins shared the same TCR beta gene
rearrangement with an identical 11 bp N region. The most plausible
interpretation of this result is that these malignancies were initiated in
one twin fetus in utero, in a single T-lineage cell that had stable
bi-allelic TCR beta rearrangements. Progeny of this cell then spread to the
other twin before birth via shared placental vasculature. This was then
followed by a 9- and 11-year preleukemic latent period before clinical
disease manifestation as leukemia or lymphoma. This result has considerable
implications for the etiology and natural history of pediatric leukemia.
Volume 89,
Issue 1,
pp. 281-285,
01/01/1997
Copyright © 1997 by The American Society of Hematology
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