Where There’s Smoke, There’s Fire: Inflammation Drives MDS

Datar, Gandhar; Goodell, Margaret A.

doi:10.1016/j.it.2020.05.007

Cited by 4 publications

(5 citation statements)

References 10 publications

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“…This review has attempted to define inflammation in order to better manage it, using an extended comparison with fire throughout as an organizing and simplifying principle for a complex topic. Lest this comparison be criticized as heavy-handed and excessive, the authors are at pains to reiterate that the Ancient Romans, in their wisdom, handed down the word inflammare, meaning to set alight or to burn, over 2000 years ago, thus inextricably linking the two words, fire and inflammation, which are often juxtaposed in the scientific literature [ 1 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

What Exactly Is Inflammation (and What Is It Not?)

Oronsky

Caroen

Reid

2022

IJMS

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In medicine, inflammation is a fuzzy, overused word first coined by the Romans, the intended meaning and precise definition of which varies according to the person and the clinical context. It tends to carry a negative connotation as a response gone awry, like a raging, out-of-control wildfire that requires immediate control and containment lest it destroy all in its path; however, frequently overlooked or lost in the shuffle is the primordial importance of inflammation to health and survival. The precise definition of inflammation matters for several reasons, not least because of the over-liberal use of anti-inflammatory drugs to inhibit inflammation, which may, contrary to prevailing dogma that all inflammation is harmful, act counterproductively to prevent restitutio ad integrum. Using fire as a central analogy, this overview attempts to define inflammation, the better to determine how to manage it, i.e., whether to fan its flames, let it burn out, or suppress it entirely.

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Section: Discussionmentioning

confidence: 99%

What Exactly Is Inflammation (and What Is It Not?)

Oronsky

Caroen

Reid

2022

IJMS

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“…In addition to inefficient hematopoiesis, a component of chronic inflammation has been consistently reported. Although the exact etiology of MDS remains elusive, emerging evidence suggests the significant involvement of innate immune signaling and inflammation in its pathogenesis [4,6,7]. Although MDS pathologies are heterogenous, a common characteristic appears to be dysregulated innate inflammation, which influences both the disease's phenotype and its progression by inducing changes in both the hematopoietic and stromal components [5].…”

Section: Inflammation Impact On Mds Hematopoiesismentioning

confidence: 99%

“…Inflammation can significantly impact HSCs' function and behavior, thereby influencing hematopoiesis [4,5]. Inflammatory signals derived from the bone marrow microenvironment impact hematopoietic stem and progenitor cells, leading to dysregulated hematopoiesis, as described in myelodysplastic syndromes (MDS) [6,7]. These conditions arise from the dysfunction of hematopoietic stem cells, resulting in the impaired differentiation and function of all types of blood cells [8].…”

Section: Introductionmentioning

confidence: 99%

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Emerging Insights into Molecular Mechanisms of Inflammation in Myelodysplastic Syndromes

Vallelonga,

Gandolfi,

Ficara

et al. 2023

Biomedicines

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Inflammation impacts human hematopoiesis across physiologic and pathologic conditions, as signals derived from the bone marrow microenvironment, such as pro-inflammatory cytokines and chemokines, have been shown to alter hematopoietic stem cell (HSCs) homeostasis. Dysregulated inflammation can skew HSC fate-related decisions, leading to aberrant hematopoiesis and potentially contributing to the pathogenesis of hematological disorders such as myelodysplastic syndromes (MDS). Recently, emerging studies have used single-cell sequencing and muti-omic approaches to investigate HSC cellular heterogeneity and gene expression in normal hematopoiesis as well as in myeloid malignancies. This review summarizes recent reports mechanistically dissecting the role of inflammatory signaling and innate immune response activation due to MDS progression. Furthermore, we highlight the growing importance of using multi-omic techniques, such as single-cell profiling and deconvolution methods, to unravel MDSs’ heterogeneity. These approaches have provided valuable insights into the patterns of clonal evolution that drive MDS progression and have elucidated the impact of inflammation on the composition of the bone marrow immune microenvironment in MDS.

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“…A series of autoimmune manifestations have been reported in a large fraction of MDS patients, and patients suffering from autoimmune diseases are at a higher risk of developing MDS [5][6][7][8][9][10]. Genetic studies of bone marrow cells also reveal that immune-related genes such as toll-interleukin 1 receptor domain containing adaptor protein (TIRAP), toll like receptor 4 (TLR4) and tumour necrosis factor receptor associated factor 6 (TRAF6) are overexpressed in MDS, activate the nuclear transcription factor-kappa B (NF-κB) signalling pathway and are implicated in numerous aspects of pathogenesis [11].…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis on mRNA microarray and microRNA microarray to screen immune-related biomarkers and pathways in myelodysplastic syndrome

et al. 2021

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Background: Myelodysplastic syndrome (MDS) is a haematopoietic malignancy that is characterized by a heterogeneous clinical course and dysplastic maturation of blood lineages. Immune dysregulation has gained attention as one of the fundamental mechanisms responsible for the development of MDS. This study aimed to screen immunerelated biomarkers and pathways in MDS. Methods: Differentially expressed mRNAs (DE-mRNAs) and differentially expressed microRNAs (DE-miRNAs) in different subtypes of MDS were sourced from the Gene Expression Omnibus (GEO) database. DE-mRNAs were intersected with immune-related gene sets to collect immune-related mRNAs, which were put into the Search Tool for the Retrieval of Interacting Genes (STRING) to construct protein-protein interaction (PPI) networks. Target mRNAs of DE-miRNAs were predicted using the miRDB database and intersected with screened immune-related mRNAs to construct miRNA-mRNA interaction networks. Topological analysis of constructed networks was applied to screen key molecules, which were assessed in independent datasets and previous literature. Enrichment analysis was applied to screen dysregulated pathways in MDS. Results: Screened key mRNAs were mainly from the Toll-like receptor (TLR) family, including TLR2, TLR4, TLR7, and from the chemokine family, including C-X-C motif chemokine ligand 10 (CXCL10) and CC chemokine ligand 4 (CCL4). Cytokine-cytokine receptor interactions were among the major pathways in the enrichment analysis results. Hsa-miR-30b, hsa-miR-30e and hsa-miR-221 were validated as key miRNAs and modulate cytokine-cytokine receptor interactions by targeting immune-related mRNAs. Conclusion: Dysregulated cytokines reflect the immunization status in MDS. Immune-related miRNA-mRNA interactions not only provide a perspective to our understanding of immunologic derangement in the pathogenesis of MDS but also provide new therapeutic opportunities.

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Where There’s Smoke, There’s Fire: Inflammation Drives MDS

Cited by 4 publications

References 10 publications

What Exactly Is Inflammation (and What Is It Not?)

What Exactly Is Inflammation (and What Is It Not?)

Emerging Insights into Molecular Mechanisms of Inflammation in Myelodysplastic Syndromes

Integrated analysis on mRNA microarray and microRNA microarray to screen immune-related biomarkers and pathways in myelodysplastic syndrome

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