Stromal bone marrow fibroblasts and mesenchymal stem cells support acute myeloid leukaemia cells and promote therapy resistance

Katerina E. Miari, Mark T. S. Williams*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)
121 Downloads (Pure)

Abstract

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.
Original languageEnglish
Pages (from-to)216-237
Number of pages22
JournalBritish Journal of Pharmacology
Volume181
Issue number2
Early online date29 Jan 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • acute myeloid leukaemia
  • AML
  • bone marrow stroma
  • fibroblasts
  • mesenchymal stem cells
  • therapeutic targeting
  • therapy resistance

ASJC Scopus subject areas

  • Pharmacology

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