Circulating miR-181a-3p, ATR, and HMGB-1 as Integrated Predictors of Induction Blast Clearance in Adults with Acute Myeloid Leukemia

Document Type : Research Articles

Authors

1 Department of Hematology and Medical Oncology, Dharmais National Cancer Centre Hospital, Jakarta, Indonesia.

2 Department of Clinical Pathology, Dharmais National Cancer Centre Hospital, Jakarta, Indonesia.

3 Department of Hematology and Medical Oncology, University of Diponegoro, Semarang, Indonesia.

4 Department of Pharmacology and Therapeutics, University of Indonesia, Jakarta, Indonesia.

5 Department of Biochemistry and Molecular Biology, University of Indonesia, Jakarta, Indonesia.

6 Department of Hematology and Medical Oncology, University of Indonesia, Jakarta, Indonesia.

7 Department of Hematology and Medical Oncology Research Unit, Dharmais National Cancer Centre Hospital, Jakarta, Indonesia.

Abstract

Methods: This study included 71 adult patients with newly diagnosed AML who received standard “7+3” induction chemotherapy. Baseline circulating miR-181a-3p and miR-181b-5p levels were quantified using quantitative real-time polymerase chain reaction, while ATM, ATR, and HMGB-1 protein levels were measured using enzyme-linked immunosorbent assay. Induction blast clearance was defined as a post-induction bone marrow blast count of <5%. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values. Associations were evaluated using Spearman correlation and relative risk (RR) with 95% confidence intervals. Results: Circulating miR-181a-3p demonstrated limited discriminatory performance (AUC = 0.564), while HMGB-1 showed modest performance (AUC = 0.615). Using ROC-derived cut-off values, low baseline miR-181a-3p expression was associated with a significantly higher likelihood of achieving induction blast clearance in monocytic AML (FAB M4–M5) (RR = 2.33, 95% CI: 1.18–4.63, p = 0.015), but not in non-monocytic subtypes. Higher ATR (RR = 1.53, 95% CI: 0.99–2.38, p = 0.047) and HMGB-1 levels (RR = 1.61, 95% CI: 1.04–2.50, p = 0.031) were also associated with improved induction response. Circulating miR-181a-3p correlated with baseline bone marrow blast percentage, suggesting its potential as a surrogate marker for leukemic burden. Conclusion: Circulating miR-181a-3p, ATR, and HMGB-1 are associated with induction blast clearance in AML, with lineage-specific effects observed for miR-181a-3p. Although the individual biomarkers demonstrated limited discriminatory performance, their integration may provide clinically relevant insights into early treatment response.

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