HMGB1 is a therapeutic target for leukemia

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein, which functions as Damage Associated Molecular Pattern molecule (DAMP) when released from cells under conditions of stress, such as injury and infection. Recent studies indicate that HMGB1 plays an important role in leukemia pathogenesis and chemotherapy resistance. Serum HMGB1 is increased in childhood acute lymphocytic leukemia as compared to healthy control and complete remission groups. Moreover, HMGB1 is a negative regulator of apoptosis in leukemia cells through regulation of Bcl-2 expression and caspase-3 activity. As a positive regulator of autophagy, intracellular HMGB1 interacts with Beclin 1 in leukemia cells leading to autophagosome formation. Additionally, exogenous HMGB1 directly induces autophagy and cell survival in leukemia cells. Experimental strategies that selectively target HMGB1 effectively reverse and prevent chemotherapy resistance in leukemia cells, suggesting that HMGB1 is a novel therapeutic target in leukemia.