Immune-biomarker signature predicts early molecular response in Iraqi chronic myeloid leukemia patients receiving front-line tyrosine-kinase inhibitors
Abstract
Chronic myeloid leukemia (CML) is characterized by ABL1::BCR-driven leukemogenesis. Although tyrosine-kinase inhib i tors (TKIs) have transformed prognosis, predicting early molecular response (EMR) and treatment-free remission (TFR) remains clinically challenging. Immune mediators such as interleukin-2 (IL)-2, IL-7, and perforin may serve as biomarkers reflecting host - leukemia interactions. This study aimed to evaluate the diagnostic and prognostic potential of IL-2, IL-7, and perforin as predictive biomarker s in Iraqi patients with CML. A total of 215 participants were enrolled, including healthy controls (n = 55), newly diagnosed CML patients (n = 20), treatment-free remission patients (TFR) (n = 20), and patients receiving imatinib (n = 30), nilotinib (n = 30), or bosutinib (n = 30). Serum IL-2, IL-7, and perforin levels were quantified by ELISA, and molecular responses were monitored using qRT-PCR standardized to the International Scale. ROC analysis determined optimal biomarker cut-offs and predictive performance for EMR and TFR. The results indicated that IL-2 and IL-7 were significantly elevated in newly diagnosed CML patients (312.4 ± 133.2 and 158.9 ± 108.4 pg/mL) compared to controls (104.6 ± 50.7 and 53.8 ± 8.1 pg/mL, P < 0.0001). Perforin was markedly reduced (1.6 ± 0.9 and 8.7 ± 5.2 ng/mL). ROC analysis revealed IL-2 (AUC = 0.980), IL-7 (AUC = 1.000), and perforin (inverse AUC < 0.00 1 ) as highly discriminative for diagnosis, while perforin (AUC = 0.999, cut-off 3.76 ng/mL) emerged as the strongest predictor of TFR. An immune - biomarker panel integrating high IL-2/IL-7 and depleted perforin at diagnosis effectively predicts EMR and sustained TFR. Incorporating immune profiling into CML ma n agement may refine early risk stratification and enable personalized TKI selection.References
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