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Emergence of Genetic Instability in Children Treated for Leukemia

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Science  21 Apr 2000:
Vol. 288, Issue 5465, pp. 514-517
DOI: 10.1126/science.288.5465.514

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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.

  • * To whom correspondence should be addressed. E-mail: finette{at}salus.med.uvm.edu

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