Hypoxia–CXCL6 axis affects arteriolar niche remodeling in acute myeloid leukemia

Li, Lijun; Man, Jiancheng; Zhao, Li

doi:10.1177/1535370220960675

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…CXCLL2 deletion from the vascular endothelial vascular niche in T cell acute lymphoblastic leukemia impeded tumor growth ( Pitt et al, 2015 ). The chemokine CXCL6 promoted angiogenesis to remodel the arteriolar niche in acute myeloid leukemia ( Li et al, 2021 ).…”

Section: Part Three: Changes In Vascular Endothelial Nichesmentioning

confidence: 99%

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

Lei

et al. 2022

Front. Physiol.

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Vascular endothelial cells, forming the inner wall of the blood vessels, participate in the body’s pathological and physiological processes of immunity, tumors, and infection. In response to an external stimulus or internal pathological changes, vascular endothelial cells can reshape their microenvironment, forming a “niche”. Current research on the vascular endothelial niche is a rapidly growing field in vascular biology. Endothelial niches not only respond to stimulation by external information but are also decisive factors that act on neighboring tissues and circulating cells. Intervention through the vascular niche is meaningful for improving the treatment of several diseases. This review aimed to summarize reported diseases affected by endothelial niches and signal molecular alterations or release within endothelial niches. We look forward to contributing knowledge to increase the understanding the signaling and mechanisms of the vascular endothelial niche in multiple diseases.

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Section: Part Three: Changes In Vascular Endothelial Nichesmentioning

confidence: 99%

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

Lei

et al. 2022

Front. Physiol.

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“…Yang et al found that IL-8 can activate Matrix Metalloproteinases (MMPs), Protein kinase B (Akt) and other downstream signaling pathways by binding CXCR1/CXCR2, and participate in the process of tumor cell proliferation and tumor angiogenesis [24] . Li et al found that the disorder of CXCL6/CXCR2 system in low hypoxia leads to inhibition of vascular remodeling and aggravate the process of vascular injury [25] . Yu et al found that CXCL5/CXCR2 can aggravate the ischemia-reperfusion injury of human microvascular endothelial cells [26] .…”

Section: Table 2: Docking Table Of Traditional Chinese Drug-ingredien...mentioning

confidence: 99%

Mechanism of Xianling Gubao Capsule in the Treatment of Steroid Induced Osteonecrosis of Femoral Head

Liu¹,

Lei²

2022

IJPS

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This study aimed to obtain the main active components of Xianling Gubao capsule and identify their pharmacological characteristics and mechanism of action in treatment of steroid-induced femoral head necrosis. The chemical constituents and direct targets of Xianling Gubao capsule were obtained by the system pharmacology platform of traditional Chinese medicine. GeneCards database and gene expression omnibus database were used to obtain pathogenic genes related to steroid-induced femoral head necrosis. Through Venn diagram software, the intersection of direct drug targets and disease-related genes was obtained to obtain the potential drug targets of Xianling Gubao capsule. In the Cytoscape 3.7.1 software, the drug component-target and protein-protein interaction networks were visualized and analyzed by network analyze plugin and molecular complex detection plugin, the degree values of nodes were analyzed to screen the core genes. Finally, the database for annotation, visualization and integrated discovery database was used for gene enrichment analysis. We obtained 76 chemical components of Xianling Gubao, 583 pathogenic related genes of steroid-induced femoral head necrosis and 38 potential drug targets of Xianling Gubao capsule for the treatment of steroid-induced femoral head necrosis. A drug componenttargets network with 1001 nodes and 3661 edges, a protein-protein interaction network with 31 nodes and 67 edges were constructed. 15 core genes were obtained by network topology analysis and enrichment analysis of potential drug targets showed that they were mainly concentrated in chemokine signaling pathway. Finally, 5 optimal drug targets of Xianling Gubao capsule for steroid-induced femoral head necrosis were obtained, respectively. Xianling Gubao capsule can prevent or treat steroid-induced femoral head necrosis by promoting the reconstruction of new capillaries after necrosis, improving intravascular coagulation, accelerating the formation of callus and regulating the differentiation and direction of bone marrow stem cells.

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“…Collectively, hypoxia is considered an adverse factor affecting the prognosis of AML ( Clarke and Fisher, 2019 ), as leukemic cells induce bone marrow hypoxia that results in the remodeling of the bone marrow niche ( Li et al, 2021a ). However, the effects of hypoxia on TIME and drug resistance in AML as well as the specific evaluation value of hypoxia-related genes in the clinical prognosis of AML remain unclear.…”

Section: Introductionmentioning

confidence: 99%

A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia

Liu,

Wang,

Kang

et al. 2024

Front. Pharmacol.

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Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with poor prognosis. Emerging evidence suggests a close association between AML progression and hypoxia. The purpose of this study was to establish a new risk prognostic model for AML based on hypoxia-related genes, and to explore the mechanisms by which hypoxia-related genes affect the prognosis of AML based on tumor immune microenvironment (TIME) and drug resistance.Methods: The AML patient samples obtained from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were classified into C1 and C2 based on hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct the model. AML patient samples were obtained from the TARGET and The Cancer Genome Atlas (TCGA) databases, serving as the training and the validation sets, and were stratified into high-risk and low-risk group according to the median risk score. The correlations between the model and TIME and anti-tumor drugs were analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive and drug-resistant cell lines were detected by Western blot and real-time PCR.Results: The C1 group with high expression of hypoxia-related genes had lower overall survival (OS). Immune-related signaling pathways were different between C1/C2, and hypoxia was positively correlated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both the training and the validation sets. The high-risk group exhibited lower OS and TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 were highly expressed in relapsed patients and AML drug-resistant cell lines.Conclusion: The established novel risk prognostic model and experiment results offer valuable insights for predicting AML prognosis and guiding drug selection. It also provides a fundamental framework for the mechanisms through which hypoxia impacts AML prognosis by modulating TIME and drug resistance.

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Hypoxia–CXCL6 axis affects arteriolar niche remodeling in acute myeloid leukemia

Cited by 7 publications

References 29 publications

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

The Role and Mechanism of the Vascular Endothelial Niche in Diseases: A Review

Mechanism of Xianling Gubao Capsule in the Treatment of Steroid Induced Osteonecrosis of Femoral Head

A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia

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