Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

We report a pair of identical twins with concordant acute lymphoblastic leu kemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which w as characterized at the DNA level by an adaptation of a long distance polym erase chain reaction (PCR) method. The genomic fusion sequence was identica l in the two leukemias, indicative of a single cell origin in one fetus, in utero. At the time twin 1 was diagnosed (aged 5 years), the bone marrow of twin 2 was hematologically normal. However, retrospective scrutiny of the DNA from an archived slide with clonotypic TEL-AML1 primers showed that the presumptive preleukemic clone was present and disseminated 9 years before a clinical diagnosis. These data provide novel insight into the natural his tory of childhood leukemia and suggest that consequent to a prenatal initia tion of a leukemic clone, most probably by TEL-AML fusion itself, the laten cy of ALL can be both extremely variable and protracted. This, in turn, is likely to reflect the timing of critical secondary events. (C) 1999 by The American Society of Hematology.