Aberrant gene expression in acute myeloid leukemia.
Published: 2006
Language: eng
Number of pages: 139
ISBN-13: 9780494219256
Description: Acute myeloid leukemia (AML) is a rapidly progressing cancer characterized by an accumulation of myeloblasts in the bone marrow and peripheral blood. AMLs are a heterogeneous group of diseases, with individual cases displaying variability in presentation, treatment response and clinical outcome. These differences can most likely be accounted for by the underlying genetic heterogeneity in leukemic cells. Though there are a number of novel therapies with the potential for improving outcome, results from ongoing trials are modest at best. While chromosomal abnormalities and genetic mutations have been identified that may be used for prognosis and as possible targets for therapy, little is known about the genetic changes involved in the progression of disease in the majority of normal karyotype patients. Furthermore, since AML most likely represents a multi-hit disease, the nature of many of the secondary hits are also unknown. It is evident that the entire list of genetic lesions in AML is far from complete. Identifying aberrantly expressed genes that contribute to the transformed nature of the hematopoietic cell will broaden our understanding of the development and progression of the disease as well as identify novel potential targets for therapy. Representational difference analysis (RDA) is a cDNA subtractive hybridization screen that I used to identify aberrantly expressed genes in AML, from which over thirty potential candidates were identified. I have chosen seven of these genes for further examination by analyzing their expression in AML cell lines and primary patient samples. The role of aberrant angiotensin expression in AML, one of the genes identified through the screen, was also investigated using a known inhibitor of its pathway in AML cells. LMO1, another gene identified from the screen, was assayed as a marker of minimal residual disease (MRD) in AML along with a panel of other MRD markers in a group of patient samples obtained at diagnosis, remission and relapse. The knowledge gained from these research studies provides the basis for further investigation involving the molecular detection of residual disease and the development of targeted therapies in AML.
Notes: Source: Dissertation Abstracts International, Volume: 68-01, Section: B, page: 0098.

Thesis (Ph.D.)--University of Toronto, 2006.

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