Identifying Leukaemic Signatures in Blood Extracellular Vesicles
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Authors
Robertson, Tristan
Date
Type
thesis
Language
eng
Keyword
Leukaemia , Cancer , Extracellular Vesicles , Biomarkers
Alternative Title
Abstract
Intercellular communication events mediated by extracellular vesicles (EVs) are becoming increasingly relevant and studied in cancer research. Although EVs are known to influence haematopoietic stem cell (HSC) proliferation and differentiation, very little is known about how EVs influence the function of HSCs or the biology of leukaemia. It is currently proposed that EVs influence the tumour microenvironment in leukaemia by inhibiting healthy hematopoiesis, while also promoting the proliferation of malignant cells. This study aimed to elucidate the composition and functionality of EVs in leukaemia patients, to better understand their role in disease. EVs were enriched using a combination of iodixanol density cushion (IDC) and size exclusion chromatography (SEC) from the blood plasma of healthy, chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) subjects. Patients with CML and AML were found to have significantly more EVs in their blood plasma than healthy controls. Colony forming cell (CFC) assays demonstrated the inhibitory effects of CML and AML EVs on the proliferation and differentiation of healthy HSCs. Single particle Raman spectroscopy and mass spectrometry were performed on healthy and leukaemic EVs to identify novel spectral and proteomic biomarkers for CML and AML. Raman spectroscopy identified unique EV profiles in samples from healthy controls, CML and AML patients, suggesting different lipid, nucleic acid, and protein content. Machine‐learning techniques were used to identify and rank EV proteins quantified by mass spectrometry, identifying potential EV protein biomarkers for leukaemia. In summary, this study has identified unique Raman spectral and protein EV signatures that distinguish normal healthy individuals from leukaemia patients and confirmed the influence of leukaemic EVs on healthy hematopoiesis.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
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Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-ShareAlike 3.0 United States
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-ShareAlike 3.0 United States