RESUMEN
The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase that functions in nucleotide excision repair of chemotherapy-induced DNA damage, the efficiency of which is predicted to be affected by a lysine to glutamine variant at codon 751. We hypothesized that this constitutive genetic variant may modify clinical response to chemotherapy, and we have examined its association with outcome following chemotherapy for acute myeloid leukemia (AML) in 341 elderly patients entered into the United Kingdom Medical Research Council AML 11 trial, and with the risk of developing chemotherapy-related AML. Among subjects treated for AML, disease-free survival at one year was 44% for lysine homozygotes, compared with 36% for heterozygotes and 16% for glutamine homozygotes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.01-1.70; P = .04). Similarly, overall survival at one year was 38% for lysine homozygotes, 35% for heterozygotes, and 23% for glutamine homozygotes (HR, 1.18; 95% CI, 0.99-1.41; P = .07). Furthermore, homozygosity for the XPD codon 751 glutamine variant was associated with a significantly increased risk of developing AML after chemotherapy (odds ratio, 2.22 for Gln/Gln vs Lys/Lys; 95% CI, 1.04-4.74). These data suggest that the XPD codon 751 glutamine variant protects against myeloid cell death after chemotherapy.
Asunto(s)
ADN Helicasas/genética , Proteínas de Unión al ADN/genética , Variación Genética , Leucemia Mieloide Aguda/epidemiología , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Codón/genética , Reparación del ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Proteína de la Xerodermia Pigmentosa del Grupo DRESUMEN
We report a patient with typical Philadelphia-chromosome-positive chronic myelocytic leukemia who developed Philadelphia-chromosome-negative acute myelocytic leukemia following autologous stem cell transplantation. The implications of this observation for disease monitoring and treatment are discussed.