Targeting integrins in drug-resistant acute myeloid leukaemia

Br J Pharmacol. 2024 Jan;181(2):295-316. doi: 10.1111/bph.16149. Epub 2023 Jun 19.

Abstract

Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that interact with not only normal haematopoietic stem cells (HSC) but also leukaemia cells like AML. There are many adhesion molecules in the BM microenvironment; therein, integrins have been of central interest. AML cells express integrins that bind to ligands in the microenvironment, enabling adhesion of leukaemia cells in the microenvironment, thereby initiating intracellular signalling pathways that are associated with cell migration, cell proliferation, survival, and drug resistance that has been described to mediate cell adhesion-mediated drug resistance (CAM-DR). Identifying and targeting integrins in AML to interrupt interactions with the microenvironment have been pursued as a strategy to overcome CAM-DR. Here, we focus on the BM microenvironment and review the role of integrins in CAM-DR of AML and discuss integrin-targeting strategies. LINKED ARTICLES: This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc.

Keywords: acute myeloid leukaemia; bone marrow microenvironment; cell adhesion molecules; cell adhesion-mediated chemoresistance; integrins; leukaemia stem cells; therapy.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Bone Marrow / metabolism
  • Cell Adhesion Molecules / metabolism
  • Hematopoietic Stem Cells
  • Humans
  • Integrins* / metabolism
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / metabolism
  • Tumor Microenvironment

Substances

  • Integrins
  • Cell Adhesion Molecules