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Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide
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 preferent...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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Sociedade Brasileira de Genética
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032972/ https://www.ncbi.nlm.nih.gov/pubmed/21637660 http://dx.doi.org/10.1590/S1415-47572009000100022 |
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author | Brassesco, María Sol Montaldi, Ana Paula Sakamoto-Hojo, Elza Tiemi |
author_facet | Brassesco, María Sol Montaldi, Ana Paula Sakamoto-Hojo, Elza Tiemi |
author_sort | Brassesco, María Sol |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3032972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Sociedade Brasileira de Genética |
record_format | MEDLINE/PubMed |
spelling | pubmed-30329722011-06-02 Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide Brassesco, María Sol Montaldi, Ana Paula Sakamoto-Hojo, Elza Tiemi Genet Mol Biol Mutagenesis 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. Sociedade Brasileira de Genética 2009 2009-03-01 /pmc/articles/PMC3032972/ /pubmed/21637660 http://dx.doi.org/10.1590/S1415-47572009000100022 Text en Copyright © 2009, Sociedade Brasileira de Genética. http://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Mutagenesis Brassesco, María Sol Montaldi, Ana Paula Sakamoto-Hojo, Elza Tiemi Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title | Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title_full | Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title_fullStr | Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title_full_unstemmed | Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title_short | Preferential induction of MLL(Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
title_sort | preferential induction of mll(mixed lineage leukemia) rearrangements in human lymphocyte cultures treated with etoposide |
topic | Mutagenesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032972/ https://www.ncbi.nlm.nih.gov/pubmed/21637660 http://dx.doi.org/10.1590/S1415-47572009000100022 |
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