Etoposide-induced apoptosis results in chromosome breaks within the <i>AF</i>9 gene: Its implication in chromosome rearrangement in leukaemia — Oak Academic Publishing
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Etoposide-induced apoptosis results in chromosome breaks within the <i>AF</i>9 gene: Its implication in chromosome rearrangement in leukaemia
Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
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Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
1 Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
2 Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Kota Samarahan, Malaysia
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, AF 9 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 AF 9 gene in both leukaemic cells and cultured normal blood cell. All the breakpoints were mapped within the BCR1 of the AF 9 gene. AF 9 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 AF 9 cleavage in K562 cells further supported the involvement of apoptosis. However, AF 9 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 AF 9 translocation are discussed.
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