miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk

Ferrer‐Marín, Francisca; Arroyo, Ana B.; Bellosillo, Beatríz; Cuenca, Ernesto J; Zamora, Lurdes; Hernández‐Rivas, Jesús María; Hernández‐Boluda, Juan‐Carlos; Fernández-Rodríguez, Concepción; Luño, Elisa; Hernández, Celsy; Kerguelen, Ana; Fiallo-Suárez, D V; Gómez-Casares, M. Teresa; Ayala, Rosa; Vélez, Patricia; Boqué, Concepción; García‐Gutiérrez, Valentín; Arrizabalaga, Beatriz; Estrada, Natàlia; Cifuentes, Rosa; Arcas, Isabel; Reyes-García, Ascensión M. de los; Besses, Carles; Vicente, Vicente; Alvarez‐Larrán, Alberto; Teruel‐Montoya, Raúl; Gónzález-Conejero, Rocío; Martı́nez, Constantino

doi:10.1038/s41375-020-0767-3

Cited by 21 publications

(25 citation statements)

References 53 publications

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“…These data suggest a role for miR-146a far beyond the mere response to an endotoxin challenge since the deficiency of this miRNA constitutively affects NF-κB signaling 30,32 . In this line, our group recently demonstrated that rs2431697 TT genotype is an early predictor of myelofibrosis progression, independent of the JAK2V617F allele burden 33 . JAK/STAT signaling pathway plays a critical role in myeloproliferative neoplasms pathogenesis by driving both the malignant clone and the inflammatory microenvironment.…”

Section: Accepted Manuscriptmentioning

confidence: 90%

“…JAK/STAT signaling pathway plays a critical role in myeloproliferative neoplasms pathogenesis by driving both the malignant clone and the inflammatory microenvironment. Thus, JAK2V617F allele burden is one of the main drivers of clonal expansion toward end-stage disease 33 . Our results showed that rs2431697 genotype increases Jak/Stat signaling, as we demonstrated in miR-146a -/mice, probably due to the elevation of systemic IL-6 levels 33,34 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

et al. 2020

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The new concept of thrombosis associated with an inflammatory process is called thromboinflammation. Indeed, both thrombosis and inflammation interplay one with the other in a feed forward manner amplifying the whole process. This pathological reaction in response to a wide variety of sterile or non-sterile stimuli eventually causes acute organ damage. In this context, neutrophils, mainly involved in eliminating pathogens as an early barrier to infection, form neutrophil extracellular traps (NETs) that are antimicrobial structures responsible of deleterious side effects such as thrombotic complications. Although NETosis mechanisms are being unraveled, there are still many regulatory elements that have to be discovered. miRNAs are important modulators of gene expression implicated in human pathophysiology almost two decades ago. Among the different miRNAs implicated in inflammation, miR-146a is of special interest because: (i) it regulates among others, TLR/NF-B axis which is of paramount importance in inflammatory processes, (ii) it regulates the formation of NETs by modifying their ageing phenotype, (iii) it has expression levels that may decrease among individuals up to 50%, controlled in part by the presence of several polymorphisms. In this manuscript, we will review the main characteristics of miR-146a biology. In addition, we will detail how miR-146a is implicated in the development of two paradigmatic diseases in which thrombosis and inflammation interact, cardiovascular diseases and sepsis, and their association with the presence of miR-146a polymorphisms and the use of miR-146a as a marker of cardiovascular diseases and sepsis.

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Section: Accepted Manuscriptmentioning

confidence: 90%

Section: Accepted Manuscriptmentioning

confidence: 99%

miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

et al. 2020

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“…miR-146a is a negative-regulator of NF-kB pathway whose levels are influenced by the rs24331697 SNP. Ferrer-Marin et al demonstrated that the rs24331697 T/T genotype, accounting for lower levels of miR-146a, is associated with post-PV/ET MF, shorter MF-free survival in ET and PV patients, and increased plasma inflammatory cytokines in MPNs [105]. These results pave the way for SNP testing in MPNs for risk stratification and outcome perdition.…”

Section: Host Genetic Variants Predisposing To Chronic Inflammatory Smentioning

confidence: 99%

Cytokine Profiling in Myeloproliferative Neoplasms: Overview on Phenotype Correlation, Outcome Prediction, and Role of Genetic Variants

Masselli

Pozzi

Gobbi

et al. 2020

Cells

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Among hematologic malignancies, the classic Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are considered a model of inflammation-related cancer development. In this context, the use of immune-modulating agents has recently expanded the MPN therapeutic scenario. Cytokines are key mediators of an auto-amplifying, detrimental cross-talk between the MPN clone and the tumor microenvironment represented by immune, stromal, and endothelial cells. This review focuses on recent advances in cytokine-profiling of MPN patients, analyzing different expression patterns among the three main Philadelphia-negative (Ph-negative) MPNs, as well as correlations with disease molecular profile, phenotype, progression, and outcome. The role of the megakaryocytic clone as the main source of cytokines, particularly in myelofibrosis, is also reviewed. Finally, we report emerging intriguing evidence on the contribution of host genetic variants to the chronic pro-inflammatory state that typifies MPNs.

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“…30,32 In this line, our group recently demonstrated that rs2431697 TT genotype is an early predictor of myelofibrosis progression, independent of the JAK2V617F allele burden. 33 Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway plays a critical role in myeloproliferative neoplasms pathogenesis by driving both the malignant clone and the inflammatory microenvironment. Thus, JAK2V617F allele burden is one of the main drivers of clonal expansion toward end-stage disease.…”

Section: Biological Functions Of Mir-146a In Immune Cellsmentioning

confidence: 99%

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2021

Thromb Haemost

View full text Add to dashboard Cite

The new concept of thrombosis associated with an inflammatory process is called thromboinflammation. Indeed, both thrombosis and inflammation interplay one with the other in a feed forward manner amplifying the whole process. This pathological reaction in response to a wide variety of sterile or non-sterile stimuli eventually causes acute organ damage. In this context, neutrophils, mainly involved in eliminating pathogens as an early barrier to infection, form neutrophil extracellular traps (NETs) that are antimicrobial structures responsible of deleterious side effects such as thrombotic complications. Although NETosis mechanisms are being unraveled, there are still many regulatory elements that have to be discovered. Micro-ribonucleic acids (miRNAs) are important modulators of gene expression implicated in human pathophysiology almost two decades ago. Among the different miRNAs implicated in inflammation, miR-146a is of special interest because: (1) it regulates among others, Toll-like receptors/nuclear factor-κB axis which is of paramount importance in inflammatory processes, (2) it regulates the formation of NETs by modifying their aging phenotype, and (3) it has expression levels that may decrease among individuals up to 50%, controlled in part by the presence of several polymorphisms. In this article, we will review the main characteristics of miR-146a biology. In addition, we will detail how miR-146a is implicated in the development of two paradigmatic diseases in which thrombosis and inflammation interact, cardiovascular diseases and sepsis, and their association with the presence of miR-146a polymorphisms and the use of miR-146a as a marker of cardiovascular diseases and sepsis.

show abstract

miR-146a rs2431697 identifies myeloproliferative neoplasm patients with higher secondary myelofibrosis progression risk

Cited by 21 publications

References 53 publications

miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

miR-146a in Cardiovascular Diseases and Sepsis: An Additional Burden in the Inflammatory Balance?

Cytokine Profiling in Myeloproliferative Neoplasms: Overview on Phenotype Correlation, Outcome Prediction, and Role of Genetic Variants

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