Tierney, Ciara (2020) Proteomic Characterisation of Patient Samples Diagnosed with Haematological Malignancies. PhD thesis, National University of Ireland Maynooth.

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Abstract

Multiple myeloma (MM) is the second most commonly diagnosed lymphoid cancer worldwide, after non-Hodgkin’s lymphoma, and is characterised by the uninhibited proliferation of terminally differentiated B-lymphocytes. The proliferation of these mutated plasma cells leads to the secretion of monoclonal proteins, resulting in mutated heavy/light chain immunoglobulin formation. Characterised by serum albumin levels, serum beta-2-microglobulin levels and hypercalcemia, renal impairment, anaemia, bone lesions (CRAB criteria), MM is diagnosed as stage Ⅰ, Ⅱ or Ⅲ. Even with a multitude of new, novel treatments developed for MM, although OS has increased significantly, MM is considered an incurable disease as the vast majority of patients go into relapse. With the use of label-free liquid chromatography mass spectrometry, proteomic analysis was carried out on MM patient samples with varying drug resistance. Vinculin, talin-1, filamin A and integrin β3 were identified as having an increased abundance in drug resistance in 4 of the 6 drugs tested. Activated RNA polymerase II transcriptional coactivator p15 118 phosphoserine and heat shock protein 27 phosphoserine 78 were identified as having a changed abundance between sensitive and resistant patients. Fatty acid binding protein 5 was detected in saliva as having a significant increase in abundance throughout disease progression of MM. Macrophage inflammatory protein 1α is predicted to play a significant role in the development of adverse side effects, after Rsq-VD treatment, with an observed increased abundance in all patients who developed toxicity throughout the clinical trial. CD44 is also predicted to have potential as a biomarker for poor outcome after Rsq-VD treatment. Multiple proteins were identified as differentially abundant in Group 1 (favourable) to Group 3 (Adverse) in acute myeloid leukaemia (AML), stromal derived growth factor 1 being of particular interest in this study. Overall this work shows proteomic techniques can be used to identify potential biomarkers for haematological malignancies.

Item Type:	Thesis (PhD)
Keywords:	Proteomic Characterisation; Patient Samples; Haematological Malignancies;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	16834
Depositing User:	IR eTheses
Date Deposited:	10 Jan 2023 15:16
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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