Reprogramming the Bone Marrow Niche: The Persistent Impact of AML Blasts on Stromal Cells and Macrophages
PhD Student
Background and Significance
Acute myeloid leukaemia (AML) is an aggressive blood cancer in which immature myeloid cells, known as blasts, proliferate uncontrollably and fail to differentiate. These blasts accumulate in the bone marrow and peripheral blood, disrupting normal blood cell production. Although many patients achieve remission, only 16.5% of people diagnosed in the UK survive five years or more, and relapse driven by chemo-resistant leukaemic cells is a major cause of treatment failure.
The bone marrow microenvironment (BMME) is increasingly linked to AML's ability to evade chemotherapy. Mesenchymal stromal cells (MSCs) are a key part of this niche and can dampen immune responses, for example by polarising macrophages towards anti-inflammatory M2-like phenotypes. AML cells can reprogram MSCs into a dysregulated state that protects leukaemia cells. Whether these changes persist once the leukaemia is cleared, and how quickly any recovery happens, remains poorly understood.
Project Aim
The aim of this project is to investigate what becomes of the changes AML causes in MSCs once the leukaemia is gone, whether they fade, how quickly, and whether prior exposure leaves the cells primed to return to a leukaemia-supporting state. By tracking these cells in parallel in a controlled model and in patient marrow, and by asking how the altered stroma continues to shape immune cells such as macrophages, we hope to identify key mediators in MSC-AML crosstalk.
Impact
With the key mediators we will identify, we hope to find ways to reset the bone marrow and prevent AML from returning by dismantling this cancer-friendly niche. This, hopefully, would help tackle AML relapse and improve patient outcomes.