Emergence of Genetic Instability in Children Treated for Leukemia

Author:

Finette B. A.123,Homans A. C.13,Albertini R. J.234

Affiliation:

1. Department of Pediatrics,

2. Department of Microbiology and Molecular Genetics,

3. Vermont Cancer Center, and

4. Department of Medicine, University of Vermont, Medical Alumni Building, Burlington, VT 05405, USA.

Abstract

T cells from patients who had received chemotherapy for B-lineage acute lymphocytic leukemia were studied to determine whether genetic instability, a principal characteristic of cancer cells, can also occur in nonmalignant cells. Consistent with expectations for a genetic instability phenotype, multiple mutations were detected in the hypoxanthine-guanine phosphoribosyltransferase ( HPRT ) reporter gene in independently isolated mutant T cells expressing identical rearranged T cell receptor β (TCRβ) gene hypervariable regions. These results indicate that cancer treatment can lead to genetic instability in nonmalignant cells in some individuals. They also suggest a mechanistic paradigm for the induction of second malignancies and drug resistance.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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5. Gatekeepers and caretakers

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