Monoclonal origin of concordant T-cell malignancy in identical twins.
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.
Ford
A M
AM
Leukaemia Research Fund Centre, Institute for Cancer Research, London, UK.
Pombo-de-Oliveira
M S
MS
McCarthy
K P
KP
MacLean
J M
JM
Carrico
K C
KC
Vincent
R F
RF
Greaves
M
M
D000483:Alleles; D001483:Base Sequence; D019070:Cell Lineage; D002648:Child; D002999:Clone Cells / Q000473:pathology*; D004200:Diseases in Twins; D005260:Female; D005330:Fetofetal Transfusion; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000473:pathology*; D014430:Twins, Monozygotic
D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta