IL-1RAP AND CD26 DYNAMICS IN MYELOID MALIGNANCIES: IMPLICATIONS FOR CHEMORESISTANCE AND THERAPEUTIC RESPONSE



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Abstract

Background: IL-1 receptor accessory protein (IL-1RAP) and CD26 drive leukemogenesis in acute and chronic myeloid leukemia (AML/CML) by supporting leukemic stem cell (LSC) survival, immune evasion, and chemoresistance. This study evaluates their expression dynamics post-chemotherapy to elucidate therapeutic implications.

Methods: Blood samples were collected from 130 individuals, including 50 AML patients (mean age: 65), 50 CML patients (64), and 30 healthy controls (46) at Al-Forat Al-Awsat Hospital (Iraq) from May 1st, 2024, to March 2nd, 2025. IL-1RAP and CD26 mRNA were quantified via qRT-PCR, and IL-1RAP protein was assessed by ELISA. Comparisons among Decitabine-treated, Cytarabine-treated, and untreated subgroups were analyzed using one-way ANOVA with Tukey's post hoc test.

Results: IL-1RAP mRNA increased in untreated CML (mean 4.01 ± 3.42 vs. control; P=0.001) and trended upward in Decitabine-treated AML (3.76 ± 1.76 vs. controls; P=0.1). IL-1RAP protein peaked in untreated AML (89.89 ± 53.53 ng/mL vs. controls 71.3 ± 24.9 ng/mL; P=0.01). CD26 mRNA were higher in untreated group (4.25 ± 1.3-fold change vs control; P = 0.001), followed by decitabine group 3.7 ± 0.81-fold change vs control; P = 0.01) and Cytarabine (364 ± 0.97-fold change vs control; P = 0.01) where in CML was (7.03 ± 4.20, P=0.0001).

Conclusions: IL-1RAP and CD26 exhibit therapy- and disease-specific regulation, with CD26 as a resilient biomarker. mRNA-protein discordance in IL-1RAP highlights post-therapeutic modulation. Combinatorial strategies (e.g., Decitabine with IL-1RAP inhibitors or CD26-targeted therapies) may overcome resistance, improving outcomes in high-risk AML/CML.

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About the authors

Mortada Hamed AL-Zobaidy

The Islamic University

Email: Mortadah033@gmail.com
ORCID iD: 0009-0006-9170-9593

MSc;

Department of Anesthesia, College of Medical Technique, The Islamic University

Iraq

Hawraa Abdulmeer Ali Al-Dahhan

University of Kufa

Author for correspondence.
Email: hawraa.aldahan@uokufa.edu.iq

PhD, Professor;

University of Kufa, Faculty of science, Pathological laboratory analysis Department

Iraq

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