How the Bone Marrow 'Neighbourhood' Fuels Blood Cancer After Treatment
This project aims to uncover the mechanisms driving the senescent phenotype observed in bone marrow stromal cells (BMSCs), with a focus on phosphoproteomic signaling pathways.
By characterising serial changes in the bone marrow (BM) microenvironment of primary cancer patients - comparing those who later develop therapy-related myeloid neoplasms (t-MN) to those who do not - we aim to identify early indicators of disease progression.
A central objective is to evaluate how an aberrant, senescent BM microenvironment contributes to clonal expansion and the eventual development of t-MN.
We will also investigate how chronic inflammation and prior exposure to cytotoxic therapy alter the BM microenvironment in patients with autoimmune rheumatic diseases and myeloid neoplasms (MN).
Another important facet of this research is to assess the influence of germline mutations on the structure and function of the BM microenvironment in MN. Additionally, we will explore how these microenvironmental changes impact outcomes of allogeneic haematopoietic stem cell transplantation in MN patients. Specific attention will be given to validating the role of a senescent BM microenvironment in driving clonal expansion in cases of clonal cytopenia of undetermined significance (CCUS) with TP53 mutations. To translate these findings into therapeutic insights, we will assess whether senolytic-targeted therapies can functionally reprogram the BM microenvironment.
Finally, we will develop a humanised ossicle model using NSG mice to evaluate the BM niche-forming capacity of BMSCs from various MN subtypes compared to healthy controls, providing a novel platform for in vivo functional validation.
Project Leader
This project is funded by the Medical Research Future Fund and Cancer Australia
SAHMRI is located on Kaurna Country. We pay respects to the Kaurna people of the Adelaide Plains and to all Aboriginal and Torres Strait Islander people. We are committed to embracing knowledge and culture as we continue our working journey to incorporate Aboriginal health research across all of our themes and further reconciliation.
Read more"Tirki nguta tappa tangka marninithi"
(Learning and knowledge are the pathway to alter the mind)
- Uncle Lewis Yerloburka O’Brien, Kaurna Elder
