The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity

Lee, Haeri; Yang, Seung-Jip; Choi, Ho Jin; Kim, Jina; Oh, Il‐Hoan

doi:10.1089/scd.2020.0166

Cited by 6 publications

(3 citation statements)

References 55 publications

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“…AML-induced BMMSC senescence seems to be a major hallmark of their reeducation process. This includes the overexpression of markers related to cell cycle arrest, ROS, DNA damage, and senescence-associated secretory phenotype (SASP) [128], with heterochromatin disorganization being one of the main drivers of leukaemia-induced BMMSC senescence [129]. Indeed, Abdul-Aziz et al [128] have described that AML-generated NOX2-derived superoxide can also trigger a pro-leukaemic p16INK4a-dependent senescence in BMMSCs.…”

Section: Bm Mesenchymal Stromal/stem Cellsmentioning

confidence: 99%

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

Mendes,

Monteiro,

Neto

et al. 2024

IJMS

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Acute myeloid leukaemia (AML) management remains a significant challenge in oncology due to its low survival rates and high post-treatment relapse rates, mainly attributed to treatment-resistant leukaemic stem cells (LSCs) residing in bone marrow (BM) niches. This review offers an in-depth analysis of AML progression, highlighting the pivotal role of extracellular vesicles (EVs) in the dynamic remodelling of BM niche intercellular communication. We explore recent advancements elucidating the mechanisms through which EVs facilitate complex crosstalk, effectively promoting AML hallmarks and drug resistance. Adopting a temporal view, we chart the evolving landscape of EV-mediated interactions within the AML niche, underscoring the transformative potential of these insights for therapeutic intervention. Furthermore, the review discusses the emerging understanding of endothelial cell subsets’ impact across BM niches in shaping AML disease progression, adding another layer of complexity to the disease progression and treatment resistance. We highlight the potential of cutting-edge methodologies, such as organ-on-chip (OoC) and single-EV analysis technologies, to provide unprecedented insights into AML–niche interactions in a human setting. Leveraging accumulated insights into AML EV signalling to reconfigure BM niches and pioneer novel approaches to decipher the EV signalling networks that fuel AML within the human context could revolutionise the development of niche-targeted therapy for leukaemia eradication.

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Section: Bm Mesenchymal Stromal/stem Cellsmentioning

confidence: 99%

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

Mendes,

Monteiro,

Neto

et al. 2024

IJMS

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“…Heterochromatin disorganization is a driver of MSC senescence [104]. AML-MSCs downregulate chromatin remodeling complex CHD1 (modulating chromatin condensation), the reduction of which is associated with a decrease in HSPCs' supportive capacity [105]. Using an integrative approach of multilevel molecular profiling combining genome-wide expression and DNA methylation high-throughput platforms, AML-MSCs were found to exhibit selective transcriptional alterations associated to epigenetic ones, including adhesions molecules, endocytosis, and metabolic pathways [23].…”

Section: Role Of Mscs In Acute Leukemiamentioning

confidence: 99%

Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers

Giallongo,

Duminuco,

Dulcamare

et al. 2023

Biomolecules

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Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Once a malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progression. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been shown that stromal cells themselves play a major role in several hematological malignancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterparts and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining the unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt tumor/MSC coupling. The present review focuses on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer progression.

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“…A decreased expression of the chromatin remodelling complex CHD1 (modulating chromatin condensation) in AML MSCs has been determined. This CHD1 reduction is associated with the loss of CFU-F and HSC supportive capacity [ 198 ]. On the other hand, the methylation status of multiple CpG sites and islands was examined in the MSCs of AML patients: 228 hypermethylated CpG site probes covering 183 gene symbols, and 523 hypomethylated CpG site probes covering 362 gene symbols were identified [ 199 ].…”

Section: The Effect Of Leukemic Cells On Mesenchymal Stem Cell Proper...mentioning

confidence: 99%

Bone Marrow Aging and the Leukaemia-Induced Senescence of Mesenchymal Stem/Stromal Cells: Exploring Similarities

Ruiz-Aparicio

Vernot

2022

JPM

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Bone marrow aging is associated with multiple cellular dysfunctions, including perturbed haematopoiesis, the propensity to haematological transformation, and the maintenance of leukaemia. It has been shown that instructive signals from different leukemic cells are delivered to stromal cells to remodel the bone marrow into a supportive leukemic niche. In particular, cellular senescence, a physiological program with both beneficial and deleterious effects on the health of the organisms, may be responsible for the increased incidence of haematological malignancies in the elderly and for the survival of diverse leukemic cells. Here, we will review the connection between BM aging and cellular senescence and the role that these processes play in leukaemia progression. Specifically, we discuss the role of mesenchymal stem cells as a central component of the supportive niche. Due to the specificity of the genetic defects present in leukaemia, one would think that bone marrow alterations would also have particular changes, making it difficult to envisage a shared therapeutic use. We have tried to summarize the coincident features present in BM stromal cells during aging and senescence and in two different leukaemias, acute myeloid leukaemia, with high frequency in the elderly, and B-acute lymphoblastic leukaemia, mainly a childhood disease. We propose that mesenchymal stem cells are similarly affected in these different leukaemias, and that the changes that we observed in terms of cellular function, redox balance, genetics and epigenetics, soluble factor repertoire and stemness are equivalent to those occurring during BM aging and cellular senescence. These coincident features may be used to explore strategies useful to treat various haematological malignancies.

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The Chromatin Remodeling Complex CHD1 Regulates the Primitive State of Mesenchymal Stromal Cells to Control Their Stem Cell Supporting Activity

Cited by 6 publications

References 55 publications

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

Transforming the Niche: The Emerging Role of Extracellular Vesicles in Acute Myeloid Leukaemia Progression

Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers

Bone Marrow Aging and the Leukaemia-Induced Senescence of Mesenchymal Stem/Stromal Cells: Exploring Similarities

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