Preferential induction of MLL (Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide

Autor(es)

Brassesco, Maria Sol ^{[1, 2]} ; Montaldi, Ana Paula ^[1] ; Sakamoto-Hojo, Elza Tiemi ^{[1, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14048900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Puericultura & Pediat, BR-14048900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Biol, BR-14048900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: GENETICS AND MOLECULAR BIOLOGY; v. 32, n. 1, p. 144-150, 2009.
• Citações Web of Science: 1

Resumo

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. (AU)

• Processo FAPESP: 03/01915-0 - Análise citogenética e molecular de translocações cromossômicas no gene MLL para avaliar os efeitos tardios da quimioterapia em linfócitos de pacientes em alta que apresentaram Leucemia Linfoide Aguda na infância
• Beneficiário: María Sol Brassesco Annichini
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 02/13317-8 - Estudo citogenetico e molecular da instabilidade genomica em resposta a lesoes induzidas no dna pela radiacao ionizante e compostos antitumorais em celulas humanas.
• Beneficiário: Elza Tiemi Sakamoto Hojo
• Modalidade de apoio: Auxílio à Pesquisa - Regular