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|Title:||ALTERNATIVE STRATEGIES IN TREATING ACUTE MYELOID LEUKAEMIA||Authors:||TAN BAN XIONG||Keywords:||Leukaemia, NPMc, p53, Mdm2, Mdm4, cell death||Issue Date:||27-Dec-2012||Citation:||TAN BAN XIONG (2012-12-27). ALTERNATIVE STRATEGIES IN TREATING ACUTE MYELOID LEUKAEMIA. ScholarBank@NUS Repository.||Abstract:||Acute myeloid leukaemia (AML) accounts for a quarter of all leukaemia and patients suffering from it have the lowest survival rates. For the past four decades, the standard chemotherapeutic treatment of AML is with anthracyclines and cytarabine, and cure rates have not improved drastically since. Unlike other cancers, there have not been any targeted treatments designed for AML that are currently in clinical use. This study focusses on the two commonly-occurring types of AML: AML with cytoplasmic mutant nucleophosmin (NPMc) and AML with wild type p53. Here, the mechanisms by which NPMc positive AML cells become resistant towards apoptosis and develop into leukaemia are investigated, and alternative means to treat the disease by targeting these mechanisms are proposed. In particular, the potential of inhibiting cytoprotective autophagy and preventing nuclear export as AML treatment are explored. Also, as more than 80% of AML are wild type for p53, this study delves into the role of Mdm4 in maintaining p53 in an inactive state and how Mdm4 downregulation is useful as a treatment for AML. In summary, this study uncovers new insights into the disease mechanisms of the two common occurrences of AML and proposes new, alternate strategies to treat these types of AML in a targeted manner.||URI:||http://scholarbank.nus.edu.sg/handle/10635/37893|
|Appears in Collections:||Ph.D Theses (Open)|
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