The Role of Integrin Beta-1 in the Chemoresistance of Acute Myeloid Leukemia

Ogana, Heather; Hurwitz, Samantha; Wan, Zesheng; Kim, Hye Na; Jambon, Samy; Abdel‐Azim, Hisham; Huang, Miller; Moeini, Babak; Heisterkamp, Nora; Carbonell, Anne-Marie; Parekh, Chintan; Konopleva, Marina; Bhojwani, Deepa; Kim, Yong-Mi

doi:10.1182/blood-2022-167902

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“…β1 integrin is an attractive target because it is the most common β subunit partner for many α subunits. Ogana and colleagues described β1‐targeted therapy with OS2966 in vitro and in vivo (Ogana et al, 2022). In xenograft mouse models with AML cell line U937 and a primary AML case, OS2966 with Ara‐C chemotherapy significantly prolongs survival compared to single agent controls.…”

Section: Integrin‐targeted Therapy In Preclinical Evaluation In Amlmentioning

confidence: 99%

Targeting integrins in drug‐resistant acute myeloid leukaemia

Ogana

Hurwitz

Wei

et al. 2023

British J Pharmacology

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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.

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Section: Integrin‐targeted Therapy In Preclinical Evaluation In Amlmentioning

confidence: 99%