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

Yuan, Shunling; Liu, Zhaoping; Xu, Zhenru; Liu, Jing; Zhang, Ji

doi:10.1186/s13045-020-00920-3

Journal of Hematology & Oncology

Table 1 Cellular functions of HMGB1 and related interactors in various types of hematopoietic malignancies

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

Tumor	Sources of HMGB1	Cellular function	Interactors and pathways	Inhibitors	References
MDS	DCs	Interacts with T cells to mediate DCs	RAGE	NR	[88]
	Plasma and BM	Impairs the ability of macrophages to phagocytose apoptotic cells	TLR4	TLR4 inhibitors	[52]
	BM	Modulates the innate immune system and inhibits apoptosis	TLRs and NF-κB pathways	HMGB1 siRNAs and sivelestat	[99]
AML	APL cell line NB4	Mediates autophagy and affects the degradation of PML-RARα	ROS, p62/SQSTM and PML-RARα	NAC	[101]
	APL	Enhances inflammation and promotes ATRA/ATO-induced DS	MEK/ERK pathways	NR	[103]
	MEL cells	Promotes MEL cells differentiation	NR	NR	[106]
	NR	Stimulates AML cells proliferation and angiogenesis	TNF-α and Tim-3	NR	[69]
	AML cells	Represses apoptosis and promotes autophagy and therapeutic resistance	Beclin-1/PI3KC3, Atg5-Atg12-Atg16	MiR-34a, MiR-181b3, MiR-142-3p	[108,109,110]
	THP cells	Promotes migration	MCP-1 and Mcl-1	GL	[111]
	Mammalian cells	Reduces adhesion	RAGE	NR	[112]
	Extracellular	Prevents necroptosis	NF-κB pathway	NR	[114]
MPN	CML cells	Promotes proliferation	COX-2, Akt/surviving and Akt/ID3 pathways	Cordycepin	[115]
	Cytoplasmic	Decreases CML cells sensitivity to anticancer drugs	JNK, ERK and Beclin-1	NR	[119]
	CML cells	Inhibits apoptosis	Bax, Bcl-2 and ROS	HMGB1 knockdown	[115]
ALL	ALL cells	Promotes inflammation	TNF-α and MAPK	NR	[122]
		Upregulates autophagy and chemoresistance	Ulk1-Atg13-FIP200 complex and Beclin1	NR	[123]
	T- and B-ALL cells	NR	NR	MiR-181a	[124]
	Pyroptosis cells	Induces cytokine release and CRS	IL-6 and GSDME	NR	[125]
CLL	CLL cells	Differentiates monocytes into NLCs	RAGE/TLR9	NR	[127]
CTCL	Peripheral blood	Promotes Th2 polarization and angiogenesis	IL-4, IL-10, IL-19 and angiogenin	NR	[130]
CTCL	Extracellular	Stimulates DLBCL cell proliferation	Src/ERK pathway	EP	[137]
ALCLs	Extracellular	Promotes the proliferation and metastasis of lymphoid cells.	NR	GL	[139]
MM	Extracellular	Promotes drug resistance, DNA damage repair and autophagy	NR	NR	[143]
	Nucleus and cytosol	Promotes autophagy and inhibits apoptosis	ubiquitination	LncRNA MALAT-1	[29]
	MM bortezomib-resistant cells	Degrades HMGB1 protein and inhibits autophagy	MEK/ERK pathway	Lycorine	[30]
	Apoptotic MM cells	Fosters an immunogenic microenvironment and promotes antitumor immunity	NR	NR	[144, 145]
	Extracellular	Acts as a thrombosis-related biomarker	NR	NR	[146, 147]

NR not reported, MPN myeloproliferative neoplasms

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