Emergence of genetic instability in children treated for leukemia.
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.
Finette
B A
BA
Department of Pediatrics, Vermont Cancer Center, University of Vermont, Medical Alumni Building, Burlington, VT 05405, USA. finette@salus.med.uvm.edu
Homans
A C
AC
Albertini
R J
RJ
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D019008:Drug Resistance, Neoplasm; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D017930:Genes, Reporter; D019672:Genes, T-Cell Receptor; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D007223:Infant; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D012008:Recurrence; D013601:T-Lymphocytes
D000970:Antineoplastic Agents; D007041:Hypoxanthine Phosphoribosyltransferase