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Blood, Vol. 94 No. 3 (August 1), 1999:
pp. 1057-1062
Protracted and Variable Latency of Acute Lymphoblastic Leukemia After
TEL-AML1 Gene Fusion In Utero
Joseph L. Wiemels,
Anthony M. Ford,
Elisabeth R. Van Wering,
Aleida Postma, and
Mel Greaves
From the Leukaemia Research Fund Centre, Institute of Cancer
Research, London, UK; the Dutch Childhood Leukemia Study Group (DCLSG),
The Hague, The Netherlands; and the Beatrix Children's Hospital,
University of Groningen, Groningen, The Netherlands.
We report a pair of identical twins with concordant acute
lymphoblastic leukemia (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 was characterized at the DNA
level by an adaptation of a long distance polymerase chain reaction (PCR) method. The genomic fusion sequence was identical 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 history of childhood leukemia and
suggest that consequent to a prenatal initiation of a leukemic clone,
most probably by TEL-AML fusion itself, the latency of ALL can
be both extremely variable and protracted. This, in turn, is likely to
reflect the timing of critical secondary events.
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