Investigating the role of the bone marrow microenvironment in multiple myeloma

Sun, Yu (2019) Investigating the role of the bone marrow microenvironment in multiple myeloma. Doctoral thesis, University of East Anglia.

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Abstract

Multiple myeloma (MM) is the second most common hematologic malignancy in the UK, characterised by uncontrolled plasma cell proliferation in the bone marrow (BM).Though the survival rate is improving, the MM incidence rate is increasing. Currently, MM is still incurable as with time malignant plasma cells inevitably become resistant to the currently available drugs. The two primary mechanisms responsible for MM relapse are through the MM cell adaptation to the treatment induced stress and through the interaction with the BM microenvironment for protection. Thus, investigations of the mechanisms of MM cell drug resistance are needed to improve the MM patient outcomes.
The aims of this PhD project were to determine: 1) how MM cells escape the endoplasmic reticulum (ER) stress induced cell death; 2) how MM cell outsource autophagy to the BM microenvironment; 3) how bone marrow stromal cell (BMSC)derived NRF2 supports MM proliferation. The results show: 1) primary MM cells exhibit high NRF2 expression; 2) high NRF2 expression reduces the ER stress induced apoptosis in MM cells; 3) MM cells induce NRF2 upregulation in BMSC; 4) primary MM cells outsource autophagy to BMSC; 5) BMSC derived NRF2 supports autophagy.
To summarise, this PhD research project has identified mechanisms through which MM cells avoid endoplasmic reticulum (ER) stress induced apoptosis and how the BMSC-MM interaction support MM cells proliferation. In identifying these mechanisms, it is hoped that further work will result in new treatment strategies forpatients with MM in the future.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Jackie Webb
Date Deposited: 20 May 2019 11:24
Last Modified: 20 May 2019 11:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/71069
DOI:

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