Dysregulation of interferon regulatory genes reinforces the concept of chronic immune response in myelodysplastic syndrome pathogenesis

Sousa, Jorge Rodrigues de; Ito, Mayumi; Costa, Marcos Benedito Caldas; Farias, Izabelle Rocha; Borges, Daniela de Paula; Taiane, None de Oliveira, Roberta; Fukutani, Kiyoshi F.; Thomé, Carolina Hassibe; Martinelli, Camila Maria da Silva; Myajima, Fabio; Vidal, Daniel Onofre; Magalhães, Sílvia Maria Meira; Figueiredo-Pontes, Lorena Lôbo de; Pinheiro, Ronald Feitosa

doi:10.1002/hon.2608

Cited by 6 publications

(2 citation statements)

References 11 publications

(15 reference statements)

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“…Notably, TLR-4, which mediates the recognition of LPS, is the best-described receptor in MDS. The constant activation of TLR-4 is associated with DNA damage induced by reactive oxygen species (ROS), generating the accumulation of genotoxic components 32 and, consequently, chromosomal abnormality 33 . Indeed, LPS activation of TLR-4 receptors may justify some inflammatory alterations observed in MDS, such as the NLRP3-mediated inflammasome activation that triggers the permanent release of pro-inflammatory cytokines such as IL-1β 34 .…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Correia Riello,

Mendonça da Silva,

Da Silva Oliveira

et al. 2024

IJHOSCR

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The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.

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Section: Discussionmentioning

confidence: 99%

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Correia Riello,

Mendonça da Silva,

Da Silva Oliveira

et al. 2024

IJHOSCR

View full text Add to dashboard Cite

show abstract

“…Notably, TLR-4, which mediates the recognition of LPS, is the best-described receptor in MDS. The constant activation of TLR-4 is associated with DNA damage induced by reactive oxygen species (ROS), generating the accumulation of genotoxic components [30], and, consequently, chromosomal abnormality [31]. Indeed, LPS activation of TLR-4 receptors may justify some inflammatory alterations observed in MDS, such as the NLRP3-mediated inflammasome activation that triggers the permanent release of pro-inflammatory cytokines such as IL-1β [32].…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota composition correlates with disease severity in myelodysplastic syndrome

Riello

Silva

Oliveira

et al. 2022

Preprint

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The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Notably, microbial signals, such as lipopolysaccharide from gram-negative bacteria can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. We sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls to test this hypothesis. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. in relation to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria in the gut of these patients.

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CircZBTB46 predicts poor prognosis and promotes disease progression of myelodysplastic syndromes and acute myeloid leukemia

Li,

Zhao,

et al. 2023

Clin Exp Med

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Dysregulation of interferon regulatory genes reinforces the concept of chronic immune response in myelodysplastic syndrome pathogenesis

Cited by 6 publications

References 11 publications

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome

Gut microbiota composition correlates with disease severity in myelodysplastic syndrome

CircZBTB46 predicts poor prognosis and promotes disease progression of myelodysplastic syndromes and acute myeloid leukemia

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