Integrin-linked kinase (ILK) in hematologic malignancies: Bridging molecular mechanisms to therapeutic innovation.

Abstract

Therapy resistance remains a formidable challenge in hematologic malignancies despite significant advances in targeted therapies. This comprehensive review examines integrin-linked kinase (ILK) as a critical molecular hub at the nexus of cell adhesion, signal transduction, and therapy resistance across leukemias, lymphomas, and multiple myeloma. Unlike in solid tumors, where ILK primarily drives invasion and metastasis, in hematologic malignancies it uniquely mediates microenvironmental protection and therapy resistance through distinct signaling networks. ILK functions as a central mediator connecting microenvironmental signals to intracellular survival pathways, with expression levels 5-20-fold higher in malignant cells compared to normal counterparts. Through systematic analysis of structural properties, expression patterns, downstream signaling, and microenvironmental interactions, we present compelling evidence for ILK as a promising therapeutic target capable of overcoming resistance mechanisms. Current data demonstrate that ILK inhibition simultaneously disrupts multiple survival pathways, sensitizes resistant cells to established therapies, and selectively targets therapy-resistant leukemic stem cells while sparing normal progenitors. This review provides a comprehensive framework for translating ILK-targeted approaches into innovative therapeutic strategies with significant potential to improve outcomes in treatment-refractory hematologic malignancies.