Investigating metabolic dependencies of acute myeloid leukaemia and state-of-the-art metabolomics development by NMR spectroscopy

Alshamleh, Islam. A. A (2022). Investigating metabolic dependencies of acute myeloid leukaemia and state-of-the-art metabolomics development by NMR spectroscopy. University of Birmingham. Ph.D.

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Abstract

The scope of this doctoral thesis is focused on identifying metabolic vulnerabilities and therapeutic targets in acute myeloid leukaemia (AML). In the course of this PhD, three main projects were carried out next to seven other collaboration projects on metabolomics profiling in health and disease. In addition, a scientific review covering current literature on metabolic reprogramming in AML was written. The first project studied the unique mitochondrial metabolism in AML caused by internal tandem duplication mutations (ITDs) of fms-like tyrosine kinase III (FLT3). This led to the identification of an essential protein (PDP1) which was validated as a putative targetable vulnerability in AML. The second part investigated amino acid dependencies in AML with a special focus on methionine. The cellular utilisation of methionine in AML was studied, as well as the molecular aspects of the dependence on exogenous methionine. Lastly, the third part addresses advancing NMR as a technology platform for metabolomics analysis by developing a real-time metabolism-imaging approach to profile metabolism of living cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):