Targeting integrins in drug‐resistant acute myeloid leukaemia

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.

Automated workflow for the cell cycle analysis of (non-)adherent cells using a machine learning approach

“…We deduce that this seeding protocol has the potential to be effectively employed with various non-adherent cell types. This is based on the principle that cell adhesion on SBS is facilitated by the nanostructure’s ability to engage with integrins (Schulte et al ., 2016), which are widely expressed in diverse cell types (Johansen et al ., 2018; Floren et al ., 2020; Kim et al ., 2020; Ogana et al ., 2023). The seeding protocol could also certainly be extended to other types of live cell imaging experiments, especially when the fluorescence intensity can be monitored for shorter durations, thereby circumventing the need for the addition of MC.…”

Cancer microenvironment and pharmacological interventions

“…Furthermore, 3D models mirror the well-established therapy resistant effects previously reported for the TME. Ogana et al (2023) discussed targeting integrins to overcome TME-elicited drug resistance in acute myeloid leukaemia (AML).…”

“…Furthermore, 3D models mirror the well‐established therapy resistant effects previously reported for the TME. Ogana et al (2023) discussed targeting integrins to overcome TME‐elicited drug resistance in acute myeloid leukaemia (AML). Although no integrin‐targeted treatments have been approved to date, this represents a potentially effective therapeutic approach not just in acute myeloid leukaemia but also for other blood cancers and solid cancers, to circumvent cell adhesion‐mediated drug resistance (CAM‐DR).…”