Identification of the molecular pathways involved in paediatric and adult acute myeloid leukaemia

Brown, Elliott

Abstract

Acute myeloid leukaemia (AML) affects 3100 people every year in the UK, around 1% of whom are under 19 years of age. Despite improvements in immunotherapeutic treatment opportunities for AML, the rates of survival particularly in adults remain poor. We wanted to determine whether adult and paediatric AML, share common molecular pathways and therefore, the same therapies could be used to treat each.
Previous dataset analysis provided a group of differentially expressed genes in different risk subgroups of AML. Using a variety of analysis tools and a comprehensive literature review, the role of these antigens and microRNAs (miRs) were investigated in various diseases and specifically AML. Models were generated using miRs as biomarkers to predict prognosis grouping based on expression and qPCR was performed to evaluate their use as a biomarker in patient sera.
Nine leukaemia associated` antigens (LAAs) and four miRs were identified for further study due to their effects on patient prognosis. Investigation of the LAAs showed potential roles in cancerous drivers and leukaemogenesis, interacting with known important pathways. Following area under the curve analysis, mRNA-sequencing data from TCGA and TARGET demonstrated that combinations of miRs made powerful predictors of prognosis. qPCR showed no significant difference in expression levels of DEmiRs in sera samples.
BIRC5 may be a key target for specific subtypes of AML and the other LAAs have been found to interact with key pathways in other cancers. However, these often have little to no research in AML patients or cell lines. Furthermore, only miR-1915-5p showed promise as a serum biomarker, however, further investigation is needed following this study.

Citation

Brown, E. Identification of the molecular pathways involved in paediatric and adult acute myeloid leukaemia. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4224412

• Thesis Type: Thesis
• Deposit Date: Nov 16, 2022
• Publicly Available Date: Feb 24, 2023
• Keywords: Biomedical sciences
• Public URL: https://hull-repository.worktribe.com/output/4224412
• Additional Information: Department of Biomedical Sciences, The University of Hull
• Award Date: Apr 1, 2022