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

Blood. 1999 Aug 1;94(3):1057-62.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Base Sequence
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit
  • Diseases in Twins*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Oncogene Proteins, Fusion*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Time Factors
  • Twins

Substances

  • Core Binding Factor Alpha 2 Subunit
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • TEL-AML1 fusion protein