Circulating miR-181a-3p, ATR, and HMGB-1 as Integrated Predictors of Induction Blast Clearance in Adults with Acute Myeloid Leukemia.
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.
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.
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.
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.
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.
Authors
Sari Sari, Setiawan Setiawan, Santosa Santosa, Louisa Louisa, Dewi Dewi, Rinaldi Rinaldi, Sutandyo Sutandyo, Cenweikiawan Cenweikiawan
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