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 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.
Leukaemia Research Fund Centre, Institute of Cancer Research, London, UK.
J L
JL
Wiemels
A M
AM
Ford
E R
ER
Van Wering
A
A
Postma
M
M
Greaves
D000293:Adolescent; D001483:Base Sequence; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D013997:Time Factors; D014427:Twins; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein