Stromal Bone Marrow Fibroblasts and Mesenchymal Stem Cells Support Acute Myeloid Leukaemia Cells and Promote Therapy Resistance.

The bone marrow (BM) is the primary site of adult haematopoiesis, where stromal elements (e.g., fibroblasts, mesenchymal stem cells/MSCs) work in concert to support blood cell development. However, the establishment of an abnormal clone can lead to a blood malignancy such as acute myeloid leukaemia (AML). Despite our increased understanding of the pathophysiology of the disease, patient survival remains suboptimal, mainly driven by the development of therapy resistance. In this review, we highlight the importance of BM fibroblasts and MSCs in health and AML and their impact on patient prognosis. We discuss how stromal elements reduce the killing effects of therapies via a combination of contact-dependent (e.g., integrins) and contact-independent (i.e., secreted factors) mechanisms, accompanied by the establishment of an immunosuppressive microenvironment. Importantly, we underline the challenges of therapeutically targeting the BM stroma to improve AML patient outcomes, due to the inherent heterogeneity of stromal cell populations.