How to say NO to vascular disruption and stem cell mobilization

Passaro, Diana; Bonnet, Dominique

doi:10.1080/14728222.2018.1486821

Cited by 4 publications

(3 citation statements)

References 24 publications

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“…Some clinical research has been devoted to the antiangiogenic effect of endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR), but to little effect, which calls researchers to reflect that the improvement of the vascular niche is far more than simply anti-angiogenesis. 9 Not only to prevent the invalid angiogenesis but also to promote the effective angiogenesis should be the direction of research for improving the vascular niches. Understanding the dynamic changes of vascular niches in time and space will help to find new treatment strategies.…”

Section: Impact Statementmentioning

confidence: 99%

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

Man

Zhao

2020

Exp Biol Med (Maywood)

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Acute myeloid leukemia (AML) is a malignant clonal disease derived from hematopoietic stem/progenitor cell. Leukemia blasts cause extensive hypoxia of bone marrow (BM), which lead to disorder and remodeling of BM niche, thereby becoming “leukemic niche” to support the development and drug-resistance of AML as well as the maintenance of normal hematopoietic stem cells. In this study, the biological characteristics (such as self-renewal, apoptosis, migration, autocrine) and function (vascularization) of mesenchymal stem cells (MSCs) and human umbilical artery endothelial cells (HUAECs) that make up BM arteriolar niche in simulated hypoxia AML context were investigated. It was found that moderate hypoxia enhanced the viability of the arteriolar niche cells, but severe hypoxia of AML BM resulted in the damage of arteriolar niche cells and the disorder of vascular cytokines C-X-C motif chemokine ligand 6 (CXCL6). The dynamic changes of CXCL6 in the system as well as its anti-apoptotic and promoting angiogenic effects suggested that CXCL6 played an important role in the remodeling of BM arteriolar niche in AML. Taking advantage of CXCL6 can save the damaged MSCs and HUAECs, which is the hope of rescuing arteriolar niche. It is suggested that CXCL6 may be an assistant strategy for microenvironment targeted therapy of AML.

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Section: Impact Statementmentioning

confidence: 99%

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

Man

Zhao

2020

Exp Biol Med (Maywood)

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“…This experimental finding may seriously limit the success of allo-HSCT by reducing the outcompetition effect of patient residual and donor-derived HSCs on the AML cell population. Therefore, studies aimed at keeping HSCs in their BM niches are warranted [120]. This goal might be achieved by considering studies that aim to reveal very specific requirements of the neoplastic cell to alter their microenvironments.…”

Section: Discussionmentioning

confidence: 99%

Targeting Leukemia Stem Cell-Niche Dynamics: A New Challenge in AML Treatment

Bernasconi

Borsani

2019

Journal of Oncology

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One of the most urgent needs in AML is to improve the disease cure rate as relapse still occurs in 60–80% of patients. Recent evidence suggests that dismal clinical outcomes may be improved by a better definition of the tight interaction between the AML cell population and the bone marrow (BM) microenvironment (“the niche”); the latter has been progressively highlighted to have an active role in the disease process. It has now been well established that the leukemic population may misinterpret niche-derived signals and remodel the niche, providing a shelter to AML cells and protecting them from the cytotoxic effects of chemoradiotherapy. Novel imaging technological advances and preclinical disease models have revealed that, due to the finite number of BM niches, leukemic stem cells (LSCs) and normal hematopoietic stem cells (HSCs) compete for the same functional areas. Thus, the removal of LSCs from the BM niche and the promotion of normal HSC engraftment should be the primary goals in antileukemic research. In addition, it is now becoming increasingly clear that AML-niche dynamics are disease stage specific. In AML, the niche has been linked to disease pathogenesis in the preleukemic stage, the niche becomes permissive once leukemic cells are established, and the niche is transformed into a self-reinforcing structure at a later disease stage. These concepts have been fostered by the demonstration that, in unrelated AML types, endosteal vessel loss occurs as a primary AML-induced niche alteration, and additional AML-induced alterations of the niche and normal hematopoiesis evolve focally and in parallel. Obviously, this endosteal vessel loss plays a fundamental role in AML pathogenesis by causing excessive vascular permeability, hypoxia, altered perfusion, and reduced drug delivery. Each of these alterations may be effectively targeted by various therapeutic procedures, but preservation of endosteal vessel integrity might be the best option for any future antileukemic treatment.

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“…Further investigations may reveal novel and useful immunotherapies. In addition, several microenvironmental targets such as IL-1β pathway and IL-1 antagonists or β3-AR agonists for sympathetic neuropathy (such as mirabegron) ( 260 ), mitochondrial heterocellular transfer, and inhibition by tigecycline, fatty acid oxidation (FAO) and FAO inhibitor etomoxir that sensitizes AML cells to therapeutic challenge, NO synthase inhibitors (such as cavtratin) ( 261 , 262 ) and endothelium activation ( 59 ), are under investigation.…”

Section: Therapies In Developmentmentioning

confidence: 99%

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

et al. 2020

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Recent studies have provided several insights into acute myeloid leukemia. Studies based on molecular biology have identified eight functional mutations involved in leukemogenesis, including driver and passenger mutations. Insight into Leukemia stem cells (LSCs) and assessment of cell surface markers have enabled characterization of LSCs from hematopoietic stem and progenitor cells. Clonal evolution has been described as having an effect similar to that of microenvironment alterations. Such biological findings have enabled the development of new targeted drugs, including drug inhibitors and monoclonal antibodies with blockage functions. Some recently approved targeted drugs have resulted in new therapeutic strategies that enhance standard intensive chemotherapy regimens as well as supportive care regimens. Besides the progress made in adoptive immunotherapy, since allogenic hematopoietic stem cell transplantation enabled the development of new T-cell transfer therapies, such as chimeric antigen receptor T-cell and transgenic TCR T-cell engineering, new promising strategies that are investigated.

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How to say NO to vascular disruption and stem cell mobilization

Cited by 4 publications

References 24 publications

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

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

Targeting Leukemia Stem Cell-Niche Dynamics: A New Challenge in AML Treatment

Acute Myeloid Leukemia: From Biology to Clinical Practices Through Development and Pre-Clinical Therapeutics

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