Preferential induction of MLL (Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide
Genet. mol. biol
;
32(1): 144-150, 2009. graf, tab, ilus
Artículo
en Inglés
| LILACS
| ID: lil-505784
ABSTRACT
Topoisomerase II inhibitors are effective chemotherapeutic agents in the treatment of cancer, in spite of being associated with the development of secondary leukemia. Our purpose was to determine the effects of etoposide on different genomic regions, aiming at discovering whether there are preferential sites which can be targeted by this drug in peripheral lymphocytes from healthy individuals. The in vitro treatment with low doses of etoposide (0.25, 0.5, and 1 µg/mL, in 1 hour-pulse or continuous-48 h treatment) induced a significant increase in chromosomal aberrations, detected by conventional staining and FISH with specific probes for chromosomes 8 and 11, compared with untreated controls (p < 0.05). Additionally, the frequencies of alterations at 11q23, detected by MLL specific probes, were significantly higher (p < 0.005) in treated cells than in controls. In contrast, an analysis of rearrangements involving the IGH gene did not disclose differences between treatments. The present results demonstrated the potential of etoposide to interact with preferential chromosome sites in human lymphocytes, even at concentrations below the mean plasma levels measured in cancer patients. This greater susceptibility to etoposide-induced cleavage may explain the more frequent involvement of MLL in treatment-related leukemia.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Leucemia
/
Proteína de la Leucemia Mieloide-Linfoide
/
Etopósido
Límite:
Adulto
/
Humanos
Idioma:
Inglés
Revista:
Genet. mol. biol
Asunto de la revista:
Genética
Año:
2009
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Brasil
Institución/País de afiliación:
Universidade de São Paulo/BR
Similares
MEDLINE
...
LILACS
LIS