Spearman, Chris (2017) 'HOXA9' as a risk factor in Acute Myeloid Leukaemia. (PhD thesis), Kingston University, .
Abstract
Acute myeloid leukaemia (AML), also known as acute myelogenous leukaemia is a cancer of the myeloid line of blood cells, characterized by the rapid proliferation of abnormal myeloid cells accumulating in the bone marrow that interfere with normal haematopoiesis. Although AML is a relatively rare disease, which accounts for almost 1% of cancer deaths in the United Kingdom and 1.2% of cancer deaths in the United States, it is the most common acute leukaemia; primarily affecting adults, and its incidence is known to increase with age. To date, there is still very little understood about the risk factors for the development of AML beyond the onset of old age. However, some key pre-existing haematological disorders such as myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPN) are now known to have a relatively high incidence of developing AML (15-52% and 7% respectively). In recent years, there have been great strides made towards understanding some of the major genetic changes that occur in AML. Normal haematopoiesis is strictly regulated by the HOX family of transcription factors which have been shown to play a key role in the development of cancer when elevated in the normal peripheral blood mononuclear cells (PBMCs) of the elderly. Together with its known role as an oncogene in AML, and a predictor of survival in this disease, it is suggested that HOXA9 expression in PBMCs could be a predictive marker of non-therapy related AML. This study suggests that elevated HOXA9 expression is indeed a predictive marker for AML development and attempts to shine a light on the progression of AML from pre-leukemic diseases such as MDS and MPN as well as offering a possible solution which may be used as a therapeutic drug either alone or in combination with current commonly used therapeutics.
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