VCAM-1 Expression on Bone Marrow Stromal Cells from Patients with Myelodysplastic Syndromes

Lubkova, O. N.; Tzvetaeva, N. V.; Momotyuk, K. S.; Belkin, V. M.; Манакова, Т. Е.

doi:10.1007/s10517-011-1248-5

Cited by 8 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VLA‐4 expression has been associated with chemoresistance in AML. It is an integrin that can bind to VCAM‐1, which is expressed by endothelial and stromal cells, as well as fibronectin (Ulyanova et al , ; Lubkova et al , ). In contrast to endothelial cells, only low levels of ICAM‐1 or VCAM‐1 are expressed on stromal cells (Peled et al , ).…”

Section: The Cxcl12/cxcr4 Axismentioning

confidence: 99%

Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia

et al. 2020

View full text Add to dashboard Cite

Summary Acute myeloid leukaemia (AML) is the most common adult acute leukaemia with the lowest survival rate. It is characterised by a build‐up of immature myeloid cells anchored in the protective niche of the bone marrow (BM) microenvironment. The CXCL12/CXCR4 axis is central to the pathogenesis of AML as it has fundamental control over AML cell adhesion into the protective BM niche, adaptation to the hypoxic environment, cellular migration and survival. High levels of CXCR4 expression are associated with poor relapse‐free and overall survival. The CXCR4 ligand, CXCL12 (SDF‐1), is expressed by multiple cells types in the BM, facilitating the adhesion and survival of the malignant clone. Blocking the CXCL12/CXCR4 axis is an attractive therapeutic strategy providing a ‘multi‐hit’ therapy that both prevents essential survival signals and releases the AML cells from the BM into the circulation. Once out of the protective niche of the BM they would be more susceptible to destruction by conventional chemotherapeutic drugs. In this review, we disentangle the diverse roles of the CXCL12/CXCR4 axis in AML. We then describe multiple CXCR4 inhibitors, including small molecules, peptides, or monoclonal antibodies, which have been developed to date and their progress in pre‐clinical and clinical trials. Finally, the review leads us to the conclusion that there is a need for further investigation into the development of a ‘multi‐hit’ therapy that targets several signalling pathways related to AML cell adhesion and maintenance in the BM.

show abstract

Section: The Cxcl12/cxcr4 Axismentioning

confidence: 99%

Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia

et al. 2020

View full text Add to dashboard Cite

show abstract

“…CXCR4 activation increases the affinity between VCAM1 expressed on the surface of MSC and its receptor VLA4, expressed by HSC and MK. Both pathways, CXCL12/CXCR4 and VCAM1/VLA4 are implicated with HSC migration (Lubkova et al . 2011; Moll and Ransohoff.…”

Section: Resultsmentioning

confidence: 99%

“…MSCs secrete the chemokine CXCL12 and Vascular Cell Adhesion molecule-1 (VCAM1) which bind to their respective receptors, CXCR4 and VLA4, expressed upon the surface of HSCs. (Lubkova et al . 2011; Liekens et al .…”

Section: Introductionmentioning

confidence: 99%

Logical modelling of myelofibrotic microenvironment predicts dysregulated progenitor stem cell crosstalk

Chapman

Duprez

Rémy

2022

Preprint

View full text Add to dashboard Cite

Primary myelofibrosis is an untreatable age-related disorder of haematopoiesis in which a break in the crosstalk between progenitor Haematopoietic Stem Cells (HSCs) and neighbouring mesenchymal stem cells causes HSCs to rapidly proliferate and migrate out of the bone marrow. 90% of patients harbour mutations in driver genes that all converge to overactivate hematopoietic JAK-STAT signalling, which is thought to be critical for disease progression, as well as microenvironment modification induced by chronic inflammation. The trigger to the initial event is unknown but dysregulated thrombopoietin (TPO) and Toll-Like Receptor (TLR) signalling are hypothesised to initiate chronic inflammation which then disrupts stem cell crosstalk. Using a systems biology approach, we have constructed an inter and intracellular logical model that captures JAK-STAT signalling and key crosstalk channels between haematopoietic and mesenchymal stem cells. The aim of the model is to decipher how TPO and TLR stimulation can perturb the bone marrow microenvironment and dysregulate stem cell crosstalk. The model predicted conditions in which the disease was averted and established for both wildtype and ectopically JAK mutated simulations. The presence of TPO and TLR are both required to disturb stem cell crosstalk and result in the disease for wildtype. TLR signalling alone was sufficient to perturb the crosstalk and drive disease progression for JAK mutated simulations. Furthermore, the model predicts the probability of disease onset for wildtype simulations that matches clinical data. These predictions might explain why patients who test negative for the JAK mutation can still be diagnosed with PMF, in which continual exposure to TPO and TLR receptor activation may trigger the initial inflammatory event that perturbs the bone marrow microenvironment and induce disease onset.

show abstract

“…The establishment of HSPCs in hematopoietic locations is mediated by the expression of CXCL12 and vascular cell adhesion molecule-1 (VCAM-1), which bind to CXCR4 and to very late antigen-4 (VLA-4), respectively (29,(38)(39)(40)(41). It is well known that, after infection, in both classical BM and EMH hematopoiesis, HSPCs are activated to produce mature lineage cells to fight pathogens.…”

Section: Establishment Of Hspcs In Hematopoietic Sitesmentioning

confidence: 99%

Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

et al. 2020

View full text Add to dashboard Cite

Cardiovascular diseases (CVDs) incidence is becoming higher. This fact is promoted by metabolic disorders such as obesity, and aging. Atherosclerosis is the underlying cause of most of these pathologies. It is a chronic inflammatory disease that begins with the progressive accumulation of lipids and fibrotic materials in the blood-vessel wall, which leads to massive leukocyte recruitment. Rupture of the fibrous cap of the atherogenic cusps is responsible for tissue ischemic events, among them myocardial infarction. Extramedullary hematopoiesis (EMH), or blood cell production outside the bone marrow (BM), occurs when the normal production of these cells is impaired (chronic hematological and genetic disorders, leukemia, etc.) or is altered by metabolic disorders, such as hypercholesterolemia, or after myocardial infarction. Recent studies indicate that the main EMH tissues (spleen, liver, adipose and lymph nodes) complement the hematopoietic function of the BM, producing circulating inflammatory cells that infiltrate into the atheroma. Indeed, the spleen, which is a secondary lymphopoietic organ with high metabolic activity, contains a reservoir of myeloid progenitors and monocytes, constituting an important source of inflammatory cells to the atherosclerotic lesion. Furthermore, the spleen also plays an important role in lipid homeostasis and immunecell selection. Interestingly, clinical evidence from splenectomized subjects shows that they are more susceptible to developing pathologies, such as dyslipidemia and atherosclerosis due to the loss of immune selection. Although CVDs represent the leading cause of death worldwide, the mechanisms involving the spleenatherosclerosis-heart axis cross-talk remain poorly characterized.

show abstract

VCAM-1 Expression on Bone Marrow Stromal Cells from Patients with Myelodysplastic Syndromes

Cited by 8 publications

References 13 publications

Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia

Dissecting the role of the CXCL12/CXCR4 axis in acute myeloid leukaemia

Logical modelling of myelofibrotic microenvironment predicts dysregulated progenitor stem cell crosstalk

Contribution of Extramedullary Hematopoiesis to Atherosclerosis. The Spleen as a Neglected Hub of Inflammatory Cells

Contact Info

Product

Resources

About