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

Genetics and Molecular Biology

María Sol Brassesco¹  Ana Paula Montaldi¹  Elza Tiemi Sakamoto-hojo¹ 

[1],Universidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de GenéticaRibeirão Preto SP ,Brazil

关键词: etoposide;    FISH;    MLL translocations;   

DOI  :  10.1590/S1415-47572009000100022

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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