Am J Blood Res 2012;2(1):36-43
Review Article
HMGB1 is a therapeutic target for leukemia
Yan Yu, Min Xie, Rui Kang, Kristen M. Livesey, Lizhi Cao, Daolin Tang
Division of Hematology, Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008,
People’s Republic of China; Division of Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA
Received October 21, 2011; accepted November 9, 2011; Epub December 15, 2011; Published January 15, 2012
Abstract: 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. (AJBR1110004).
Keywords: HMGB1, leukemia, apoptosis, autophagy, chemotherapy
Full Text PDF
Address all correspondence to:
Daolin Tang, MD, PhD
Department of Surgery, University of Pittsburgh
G.21, Hillman Cancer Center, 5117 Centre Ave
Pittsburgh PA, 15213, USA;
Tel: 01-412-623-1211, Fax: 01-412-623-1212.
E-mail: tangd2@upmc.edu;
Lizhi Cao, MD
Department of Pediatrics, Xiangya Hospital
Central South University
110 Xiangya Road Changsha
Hunan 410008, People’s Republic of China.
Tel: 86-731-84327208, Fax: 86-731-84327332
E-mail: lizhicao@gmail.com
Review Article
HMGB1 is a therapeutic target for leukemia
Yan Yu, Min Xie, Rui Kang, Kristen M. Livesey, Lizhi Cao, Daolin Tang
Division of Hematology, Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008,
People’s Republic of China; Division of Oncology, Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA
Received October 21, 2011; accepted November 9, 2011; Epub December 15, 2011; Published January 15, 2012
Abstract: 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. (AJBR1110004).
Keywords: HMGB1, leukemia, apoptosis, autophagy, chemotherapy
Full Text PDF
Address all correspondence to:
Daolin Tang, MD, PhD
Department of Surgery, University of Pittsburgh
G.21, Hillman Cancer Center, 5117 Centre Ave
Pittsburgh PA, 15213, USA;
Tel: 01-412-623-1211, Fax: 01-412-623-1212.
E-mail: tangd2@upmc.edu;
Lizhi Cao, MD
Department of Pediatrics, Xiangya Hospital
Central South University
110 Xiangya Road Changsha
Hunan 410008, People’s Republic of China.
Tel: 86-731-84327208, Fax: 86-731-84327332
E-mail: lizhicao@gmail.com
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