High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

Abstract

High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.

HMGB1 in inflammation and cancer

“…At the membrane, HMGB1 promotes axonal sprouting and neurite growth. HMGB1 can be transferred to extracellular context by two ways: active secretion from immunocompetent cells or passive release from apoptotic or necrotic cells, participating in immune responses autophagy and inhibits apoptosis of tumor cells to induce chemotherapy resistance [15]. On the other hand, HMGB1 plays a protective role in the suppression of tumor and tumor chemoradiotherapy and immunotherapy.…”

“…But it remains to be studied whether HMGB1 interacts with other tumor suppressors or oncoproteins. Extracellular HMGB1 enhances chemotherapy efficacy by transforming tumor cells from apoptosis to senescence [15]. In addition, HMGB1 can mediate immunogenic cell death during chemoradiotherapy and enhance anti-tumor immunity.…”

“…Extracellular HMGB1 promotes the release of cytokines such as IL-6 and IL-8 by activating MAPK- and MyD88-dependent NF-κB pathways, which in turn stimulates tumor cells proliferation, angiogenesis, EMT, invasion, and metastasis. Nucleus and cytoplasmic HMGB1 promotes autophagy and inhibits apoptosis of tumor cells to induce chemotherapy resistance [ 15 ]. On the other hand, HMGB1 plays a protective role in the suppression of tumor and tumor chemoradiotherapy and immunotherapy.…”

Extracellular HMGB1 Interacts with RAGE and Promotes Chemoresistance in Acute Leukemia Cells

“…HMGB1 is a highly conserved nuclear protein that has been proven to be upregulated in various kinds of cancers. Studies demonstrated that HMGB1 was over-expressed in three leukemia cell lines K562,HL60 and Jurkat) and was correlated to the stage of leukemia [20,21] . And it is reported that the expression of HMGB1 in primary and relapsed leukemia was much higher than healthy people and patients with complete remission [22] .…”

Panax ginseng-Derived Extracellular Vesicles Facilitate Anti-Senescence Effects in Human Skin Cells: An Eco-Friendly and Sustainable Way to Use Ginseng Substances

“…Therefore, besides the proposed role in lymphocyte membrane invagination [75,76], DG associated with GEVs may evoke responses in human skin cells by activating PKC signaling, thereby mediating inter-cellular communication between plant and human cells. Given that PKC can in turn regulate HMGB1 activity via phosphorylation [77], the increased intracellular expression of HMGB1 in GEV-treated melanocytes may be partially attributable to vesicular DG-activated PKC signaling. Thus, it may be worth investigating whether GEVs can activate PKC signaling and whether inhibition of that signaling can eliminate GEV-induced anti-senescence phenotypes in human melanocytes.…”