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 and 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 bone marrow fibroblasts and MSCs in health and acute myeloid leukaemia 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 bone marrow stroma to improve acute myeloid leukaemia patient outcomes, due to the inherent heterogeneity of stromal cell populations.

Automated summary

The bone marrow plays a vital role in adult hematopoiesis, but abnormalities in stromal elements such as fibroblasts and MSCs can lead to blood malignancies like AML. This review emphasizes the significance of bone marrow fibroblasts and MSCs in both health and AML, and their impact on patient prognosis. The review also discusses how stromal elements contribute to therapy resistance by creating an immunosuppressive microenvironment, making it challenging to target the bone marrow stroma for improved AML outcomes.