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Published on: March 5, 2018
Baseline Extracellular HMGB-1 Levels Associated with Induction Chemotherapy Response in Adult Acute Myeloid Leukemia
Resti Mulya Sari1, Lyana Setiawan2, Damai Santosa3
1Division of Hematology and Medical Oncology, Dharmais Cancer Hospital, Jakarta, Indonesia.
Background:
Treatment response in acute myeloid leukemia (AML) is influenced by multiple biological and molecular mechanisms. High-mobility group box 1 (HMGB-1) is involved in inflammation, autophagy, apoptosis, and immunogenic cell death. This study evaluated associations of baseline circulating miR-181a-3p, miR-181b-5p, ATM, ATR, and HMGB-1 with successful induction response in adults with newly diagnosed AML.
Methods:
This prospective cohort study was conducted at two referral hospitals in Jakarta, Indonesia. Adults with newly diagnosed AML receiving standard D3A7 induction chemotherapy were enrolled consecutively. Baseline miR-181a-3p and miR-181b-5p were quantified using digital polymerase chain reaction, whereas ATM, ATR, and HMGB-1 were measured using enzyme-linked immunosorbent assays before chemotherapy. Successful induction response was assessed by clinical and bone marrow evaluation after induction. Receiver operating characteristic analysis determined an exploratory HMGB-1 cut-off. Associations were evaluated using relative risks (RRs) with 95% confidence intervals (CIs).
Results:
Among 102 patients initiating induction chemotherapy, 25 died during induction or early post-induction care. The biomarker-evaluable cohort comprised 71 patients, of whom 40 (56.3%) achieved a successful response. Baseline miR-181a-3p, miR-181b-5p, ATM, and ATR were not significantly associated with response. HMGB-1 yielded an area under the curve of 0.615 (95% CI, 0.480-0.749). The exploratory cut-off was 28.59 pg/mL, with 65.0% sensitivity and 61.3% specificity. Low HMGB-1 was associated with a lower probability of successful response (RR, 0.620; 95% CI, 0.394-0.975; p = 0.038). In the final clinical-biomolecular model, high HMGB-1 remained associated with successful response after adjustment for platelet count and ATR (adjusted RR, 1.666; 95% CI, 1.092-2.541; p = 0.018).
Conclusion:
Low baseline circulating HMGB-1 was associated with a lower probability of successful induction response in the biomarker-evaluable adult AML cohort. Given its modest discriminatory performance and internally derived cut-off, HMGB-1 should be considered an exploratory complementary biomarker requiring external validation and serial evaluation.
