Serum soluble CD25, Galectin-9, and CXCL9 as immunological markers differentiating complete remission from refractory
Abdullah Salim Al-Karawi1, Ali Saad Al-Budairi2, Ali M Atoom3
1Department of Microbiology, College of Science, Mustansiriyah University, Baghdad, Iraq.
Background:
Acute myeloid leukemia (AML) remains an aggressive hematologic malignancy with heterogeneous responses to induction chemotherapy. Reliable biomarkers to distinguish patients achieving complete remission (CR) from those with refractory disease are needed to support immunological assessment of treatment response.
Objective:
To evaluate whether serum soluble CD25 (sCD25), galectin-9 (Gal-9), and CXCL9 differ between AML patients in CR, refractory AML patients, and healthy controls, and to assess their discriminative performance for refractory versus CR status.
Methods:
In this single-center case-control study, 155 participants were enrolled (50 healthy controls, 55 AMLCR, 50 AML-Refractory). Serum sCD25, Gal-9, and CXCL9 were quantified by sandwich ELISA. Between-group comparisons used the Kruskal-Wallis test with Dunn post-hoc pairwise contrasts; p-values were adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR). Discriminative performance was evaluated by receiver operating characteristic (ROC) analysis with bootstrap-derived 95% confidence intervals (1000 resamples), and pairwise AUC comparisons were performed using DeLong's test.
Results:
Serum sCD25 and Gal-9 were significantly elevated in refractory patients compared with CR and controls (adjusted p < 0.001 for both), whereas CXCL9 was highest in the CR group and lowest in refractory patients (adjusted p < 0.001). For discrimination between refractory and CR status, CXCL9 showed the highest single-marker performance (AUC = 0.94, 95% CI: 0.90-0.98), followed by sCD25 (AUC = 0.91, 95% CI: 0.86-0.96) and Gal-9 (AUC = 0.89, 95% CI: 0.83-0.94). A combined logistic regression model incorporating all three markers yielded cross-validated AUC = 0.96 (95% CI: 0.93-0.99); the improvement over CXCL9 alone did not reach statistical significance (DeLong p = 0.31).
Conclusion:
sCD25, Gal-9, and CXCL9 collectively describe two complementary immunological axes in AML chronic activation/exhaustion (sCD25, Gal-9) and effector-cell trafficking (CXCL9) and robustly discriminate refractory from remission status in this cross-sectional cohort. Prospective longitudinal studies are required before these markers can be recommended for prognostic use or clinical decision-making.
Clinical Significance:
The present study identifies a reproducible serum biomarker panel (sCD25, Galectin-9, and CXCL9) that reflects the dynamic balance between immune activation and exhaustion in acute myeloid leukemia (AML). The combined measurement of these markers can distinguish patients in complete remission from those with refractory disease, correlating with treatment response and residual immune dysregulation. These findings highlight a practical, non-invasive immunological tool that could support early detection of relapses, guide therapeutic monitoring, and enhance risk stratification in AML management.
