Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia
Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is the most common partner gene of MLL. AF9 shares similar structural element with the M...
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| Format: | Article |
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Scientific Research Publishing
2012
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| Online Access: | http://ir.unimas.my/id/eprint/8232/ |
| _version_ | 1848836330746806272 |
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| author | Cynthia Patricia, Nicholas Sim, S.P |
| author_facet | Cynthia Patricia, Nicholas Sim, S.P |
| author_sort | Cynthia Patricia, Nicholas |
| building | UNIMAS Institutional Repository |
| collection | Online Access |
| description | Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is the most common partner gene of MLL. AF9 shares similar structural element with the MLL gene. Various mechanisms of translocation have been proposed for the MLL gene, including apoptosis, particularly the apoptotic nuclease. In the current study, we show that VP-16 induced cleavage of the AF9 gene in both leukaemic cells and cultured normal blood cell. All the breakpoints were mapped within the BCR1 of the AF9 gene. AF9 cleavages in leukaemic cells were abolished by pre-treatment with caspase inhibitor (Z-DEVD-FMK), suggesting the involvement of caspase-activated DNase (CAD). The absence of AF9 cleavage in K562 cells further supported the involvement of apoptosis. However, AF9 cleavages in cultured normal blood cell were not eliminated by caspase inhibitor. The possible role of CAD and other apoptotic nucleases/effectors that could be involved in AF9 translocation are discussed. |
| first_indexed | 2025-11-15T06:22:03Z |
| format | Article |
| id | unimas-8232 |
| institution | Universiti Malaysia Sarawak |
| institution_category | Local University |
| last_indexed | 2025-11-15T06:22:03Z |
| publishDate | 2012 |
| publisher | Scientific Research Publishing |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | unimas-82322015-07-03T02:41:34Z http://ir.unimas.my/id/eprint/8232/ Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia Cynthia Patricia, Nicholas Sim, S.P R Medicine (General) Treatment with etoposide (VP-16) has been associated with translocation of the mixed lineage leukaemia (MLL) gene seen in treatment-related acute myeloid leukaemia (t-AML). Among the different partner genes, AF9 is the most common partner gene of MLL. AF9 shares similar structural element with the MLL gene. Various mechanisms of translocation have been proposed for the MLL gene, including apoptosis, particularly the apoptotic nuclease. In the current study, we show that VP-16 induced cleavage of the AF9 gene in both leukaemic cells and cultured normal blood cell. All the breakpoints were mapped within the BCR1 of the AF9 gene. AF9 cleavages in leukaemic cells were abolished by pre-treatment with caspase inhibitor (Z-DEVD-FMK), suggesting the involvement of caspase-activated DNase (CAD). The absence of AF9 cleavage in K562 cells further supported the involvement of apoptosis. However, AF9 cleavages in cultured normal blood cell were not eliminated by caspase inhibitor. The possible role of CAD and other apoptotic nucleases/effectors that could be involved in AF9 translocation are discussed. Scientific Research Publishing 2012 Article PeerReviewed Cynthia Patricia, Nicholas and Sim, S.P (2012) Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia. Advances in Bioscience and Biotechnology, 3 (6). pp. 686-694. http://www.scirp.org/journal/PaperInformation.aspx?PaperID=23653#.VZX17RvzqM8 10.4236/abb.2012.326089 |
| spellingShingle | R Medicine (General) Cynthia Patricia, Nicholas Sim, S.P Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title | Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title_full | Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title_fullStr | Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title_full_unstemmed | Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title_short | Etoposide-induced apoptosis results in chromosome breaks within the AF9 gene: Its implication in chromosome rearrangement in leukaemia |
| title_sort | etoposide-induced apoptosis results in chromosome breaks within the af9 gene: its implication in chromosome rearrangement in leukaemia |
| topic | R Medicine (General) |
| url | http://ir.unimas.my/id/eprint/8232/ http://ir.unimas.my/id/eprint/8232/ http://ir.unimas.my/id/eprint/8232/ |