Omer Qutaiba B. Allela
1* 
, Abdulkareem Shareef
2, Ashishkumar Kyada
3, H. Malathi
4, Laxmidhar Maharana
5, Dinesh Puri
6,7, Harshit Gupta
8, Djamila Polatova
9, Hayder Naji Sameer
10, Ahmed Yaseen
11, Zainab H. Athab
12, Mohaned Adil
131 College of Pharmacy, Alnoor University, Mosul, Iraq
2 Ahl al bayt University, Kerbala, Iraq
3 Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, Gujarat, India
4 Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India
5 Department of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha-751030, India
6 Department of Pharmacy, Graphic Era Hill University, Dehradun, India
7 Centre for Promotion of Research, Graphic Era Deemed to be University, Dehradun, Uttarakhand-248002, India
8 Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, 140401, Punjab, India
9 Scientific-Practical Medical Center for Pediatric Oncology, Hematology and Immunology, Tashkent, Uzbekistan
10 Collage of Pharmacy, National University of Science and Technology, Dhi Qar, 64001, Iraq
11 Gilgamesh Ahliya University, Baghdad, Iraq
12 Department of Pharmacy, Al-Zahrawi University College, Karbala, Iraq
13 Pharmacy College, Al-Farahidi University, Baghdad, Iraq
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.