Investigation of the role of marrow adipose tissue in the acute myeloid leukaemia bone marrow microenvironment.

Shafat, Manar (2017) Investigation of the role of marrow adipose tissue in the acute myeloid leukaemia bone marrow microenvironment. Doctoral thesis, University of East Anglia.

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Abstract

Acute myeloid leukaemia (AML) is a cancer of the blood forming cells of the bone marrow (BM) and has a high mortality rate in the elderly population. New, tolerable therapeutic strategies are necessary for reducing the mortality rate associated with AML in this fragile, less fit population. The tumour microenvironment is an evolving target in the search for lower chemotherapy-induced toxicity and strategies that can encompass a larger sector of the population including the elderly. Adipocytes in the BM were long considered to be mere occupants however, emerging research has identified these cells to be more than such and have an active role in metabolism regulation and an endocrine organ in its own right. In the context of cancers, adipocytes now pose an attractive target for novel cancer treatments due to their ability to confer chemoresistance in the tumour microenvironment. Here, I show the active participation of adipocytes that enhance the survival and proliferation of the AMLs within the BM microenvironment (BMM) though the support of several cellular functions in the AMLs. I also show that adipocytes support metabolism of AML by providing them with energy substrates in the form of fatty acid which are then used to support the proliferation of the AMLs. Additionally, I provide preliminary results implicating genes that may be responsible for the homing and free fatty acquisition in the BMM. These findings therefore provide important pre-clinical evidence for targeting factors in the BMM that support the tumour survival which may be less toxic than current therapies that do not encompass the wider AML population.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Bruce Beckett
Date Deposited: 23 Jul 2018 08:38
Last Modified: 23 Jul 2018 08:38
URI: https://ueaeprints.uea.ac.uk/id/eprint/67750
DOI:

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