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 beta (TCRbeta) 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adolescent
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Adult
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Alleles
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Antineoplastic Agents / therapeutic use*
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Burkitt Lymphoma / blood
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Burkitt Lymphoma / drug therapy*
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Burkitt Lymphoma / genetics*
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Cell Lineage
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Cell Transformation, Neoplastic
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Child
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Child, Preschool
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Clone Cells
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Drug Resistance, Neoplasm
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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Genes, Reporter
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Genes, T-Cell Receptor*
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Humans
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Hypoxanthine Phosphoribosyltransferase / genetics
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Infant
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Mutation*
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Neoplasms, Second Primary / etiology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Recurrence
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T-Lymphocytes*
Substances
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Antineoplastic Agents
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Hypoxanthine Phosphoribosyltransferase