Mechanisms and consequences of constitutive activation of integrin-linked kinase in acute myeloid leukemia

• Published in: Cytokine & growth factor reviews Vol. 43; pp. 1 - 7
• Main Authors: Alasseiri, Mohammed, Ahmed, Afsar U., Williams, Bryan R.G.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2018
• Subjects: Acute myeloid leukemia; Cell signaling; Cytokines; Hematopoiesis; Integrin-linked kinase; Therapeutics; Integrin-linked kinase; Cytokines; Hematopoiesis; Acute myeloid leukemia; Cell signaling; Therapeutics
• ISSN: 1359-6101; 1879-0305
• DOI: 10.1016/j.cytogfr.2018.06.001

[Display omitted] •ILK signaling is important for the normal functioning of immune cells and hematopoietic cells.•ILK regulates the production of proinflammatory cytokines.•ILK signaling is commonly deregulated in acute myeloid leukemia.•Targeting ILK may be a novel therapeutic approach in the treatment of AML. Integrin-linked kinase (ILK) has emerged as a critical adaptor and mediator protein in cell signaling pathways that is commonly deregulated in acute myeloid leukemia (AML). This has led to the expectation that therapeutic targeting of ILK may be a useful option in treating leukemia. Although ILK can regulate many cellular processes, including cell differentiation, survival, migration, apoptosis and production of pro-inflammatory cytokines, its role in promoting AML is still unclear. However, its ability to mediate phosphorylation and regulate the important hematopoietic stem cell regulators protein kinase B (AKT) and glycogen synthase kinase-3β supports ILK as an attractive target for the development of novel anticancer therapeutics. In this review, we summarize the existing knowledge of ILK signaling and its impact on cytokines, paying particular attention to the relevance of ILK signaling in AML. We also discuss the rationale for targeting ILK in the treatment of AML and conclude with perspectives on the future of ILK-targeted therapy in AML.