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Oxidative stress in myelodysplastic syndromes

ABSTRACT: Control of oxidative stress in the bone marrow (BM) is key for maintaining the balance between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an oxidative stress marker in BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox.

INSTRUMENT(S): 4800 Plus MALDI TOF/TOF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bone Marrow

DISEASE(S): Myelodysplastic Syndrome

SUBMITTER: Alba Rodriguez

LAB HEAD: Joaquín Martínez

PROVIDER: PXD013609 | Pride | 2019-10-30

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	164330099_ImagenGel2D.pptx	Other
	F020818.dat	Other
	F020818.mgf	Mgf
	F020818.mzML	Mzml
	F020818.mzid	Mzid

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1 - 5 of 22

Publications

Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy.

Rodríguez-García Alba A Morales María Luz ML Garrido-García Vanesa V García-Baquero Irene I Leivas Alejandra A Carreño-Tarragona Gonzalo G Sánchez Ricardo R Arenas Alicia A Cedena Teresa T Ayala Rosa María RM Bautista José M JM Martínez-López Joaquín J Linares María M

Antioxidants (Basel, Switzerland) 20191024 11

Control of oxidative stress in the bone marrow (BM) is key for maintaining the interplay between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an indicator of oxidative stress in the BM of patients with MDS and control subjects, and also patie ...[more]

PMID: 31652983

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Bulk RNA sequencing of Bone Marrow Endothelial Progenitor Cells from Patients with Myelodysplastic Syndromes

Project description:Myelodysplastic syndromes(MDS) are a group of heterogeneous disease. Emerging evidence has shown the bone marrow(BM) endothelial progenitor cells(EPCs) are also heterogeneity. To uncover the underlying mechanism of heterogeneous BM EPCs in different types of MDS patients. RNA sequencing(RNA-seq) analyses were performed to analyse BM EPCs at day 7 in culture from lower-risk MDS(N=3), higher-risk MDS(N=3), acute myloid leukemia(AML) patients(N=3) and healthy donors(HDs)(N=3). We analysed the hematopoiesis- and immune-related genes and pathways.

2022-04-06 | GSE197907 | GEO

Mesenchymal stem cells from myelodysplastic syndromes are functionally and genomically abnormal

Project description:Myelodysplastic syndromes (MDS) are a group of clonal disorders of hematopoietic stem cells. Mesenchymal stem cells (MSC) are the progenitors of the Bone Marrow (BM) stroma and have been involved in the physiopathology of MDS. The presence of cytogenetic aberrations on MSC from MDS patients is controversial. The aim of the study is to characterize BM derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridisation (FISH) analysis and genetic changes by array based comparative genomic hybridization (array-CGH). 32 cases of untreated MDS were included in the study. MSC from MDS achieved confluence at a slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was also lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic, and gains were more frequent than looses. The results of array-CGH were confirmed by FISH. When an unsupervised hierarchical cluster analysis was performed two clusters were identified: one of them included the 5q- syndrome patients, while the other incorporated the rest of the MDS patients. Our results shows, for the first time, that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to particular MDS subtypes. Keywords: Genomic comparison between mesenchymal cells

2008-08-01 | GSE10822 | GEO

Gene expression profiling in myelodysplastic syndromes

Project description:Myelodysplastic syndromes (MDS) are a heterogenous group of hematopoietic stem cell disorders characterized by dysplastic blood cell formation and peripheral blood cytopenias. Up to 30% of patients with MDS will progress to a highly chemotherapy-resistant secondary acute myeloid leukemia (sAML). We identified mutations in U2AF1 in MDS patients and patients with U2AF1 mutations are at an increased risk of developing sAML. We identified mutations in U2AF1 in patients with MDS and hypothesized that U2AF1 mutations may represent a novel mechanism that could alter gene expression in MDS. To elucidate gene expression changes associated with U2AF1 mutations, we analyzed the global mRNA expression profile obtained from bone marrow CD34+ cells purified from 5 MDS patients with a U2AF1 mutation, 10 MDS patients without a mutation, and 4 normal donors.

2011-11-23 | E-GEOD-30195 | biostudies-arrayexpress

DNA Replication Stress Due to Loss of R-Loops in Myelodysplastic Syndromes with SF3B1 Mutation

Project description:Myelodysplastic syndromes (MDS) with mutated SF3B1 gene have many features including a favorable outcome that are distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we show that SF3B1-mutated MDS are characterized by a dramatically reduced R-loop formation predominating in gene bodies, which tightly associates with reduced retention of introns specifically found in SF3B1-mutated, but not in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibited augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation, which were recapitulated in murine Sf3b1K700E/+ proerythroblasts. Importantly, R-loop formation was restored by histone deacetylase inhibition using SAHA/vorinostat, which improved Sf3b1K700E/+ erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress is a hallmark of SF3B1- mutated MDS ineffective erythropoiesis, which could be used as a new therapeutic target.

2024-04-08 | PXD038700 | Pride

DNA Replication Stress Due to Loss of R-Loops in Myelodysplastic Syndromes with SF3B1 Mutation

2024-05-29 | PXD038656 | Pride

miRNA expression profile analysis in myelodysplastic syndromes

Project description:The miRNA-related signaling pathways in MDS could be screened using high throughput bioinformatics analysis based on the miRNAs expression profile network. Here, we tried to identify the miRNAs-regulated pathways through a miRNA microarray in CD34+ cells from MDS patients. miRNA expression profile analysis was performed in 12 MDS patients and 6 normal controls using GeneChipÂ® miRNA 3.0 Array, and diffirential miRNAs were identified.

2016-06-30 | E-GEOD-81372 | biostudies-arrayexpress

Gene expression profile analysis in myelodysplastic syndromes

Project description:The pathogenesis-related signaling pathways in MDS could be screened using high throughput bioinformatics analysis based on the gene expression profile network. Here, we tried to identify the mRNAs-regulated pathways through a mRNA microarray in CD34+ cells from MDS patients. Gene expression profile analysis was performed in 12 MDS patients and 6 normal controls using GeneChipÂ® PrimeViewâ?¢ Human Gene Expression Array, and diffirential genes were identified.

2016-06-30 | E-GEOD-81173 | biostudies-arrayexpress

Characterization and Targeting of Malignant Stem Cells in Patients with Advanced Myelodysplastic Syndromes (MDS) [drug]

Project description:In this study we report that during evolution of MDS malignant HSCs activate distinct cellular programs that render such cells susceptible to therapeutic intervention. Specifically, metabolic analyses of the MDS stem cell compartment shows a profound activation of protein synthesis machinery and increased oxidative phosphorylation that occurs during later stages of MDS pathogenesis. Reliance on protein synthesis makes MDS stem cells senstive to translation inhibitors including homoharringtonine.

2018-08-01 | GSE116099 | GEO

Protein Array Screening of Myelodysplastic Syndromes I

Project description:In a two-stage study we investigated levels of Immunoglobulin G (IgG) reactivity in plasma from Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) post MDS patients (59 and 16 cases respectively) as compared to healthy cohort (34). In Stage I we utilized high-throughput protein arrays (23 232 total signals, in duplicate) to identify proteins of high-interest. In Stage II we designed new protein arrays (352 total signals, in duplicate) to further focus on 25 of the proteins from Stage I and expanded to a larger cohort, including both male and female samples (161 MDS and 43 AML patients; 112 healthy controls). Stage I resulted in 35 proteins displaying increased IgG reactivity in patients as compared to the healthy controls (P< 4.3 x10-07, Bonferroni Corrected P<0.01). This protein subset included 14 proteins associated with cancer, 12 with apoptosis, and 3 with the NFAT Regulation canonical pathway. Using the focused arrays we performed a classification of MDS patients and healthy controls. Stage II subsequently identified a high-interest focused set of 3 proteins, namely AKT3, FCGR3A and ARL8B displaying aberrant increased reactivity in patient subgroups, in concordance with Stage I. Autoantibody reactivity against specific proteins provides complementary information to other known molecular signatures for MDS and may enhance our capabilities for detecting and classifying MDS. In the study presented here, MDS patients were classified into Stable, Transforming or AML post MDS (L) classes retrospectively. The different patients were compared to a healthy cohort to assess increased autoantibody reactivity to specific patients as opposed to healthy groups Stage 1 of Study: 111 Files Analyzed, 37 sMDS, 22 tMDS, 16 AML(L), 34 Healthy and 2 Negative Controls (used to eliminate non-plasma signals)

2013-11-21 | E-GEOD-48153 | biostudies-arrayexpress

Protein Array Screening of Myelodysplastic Syndromes II

Project description:In a two-stage study we investigated levels of Immunoglobulin G (IgG) reactivity in plasma from Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) post MDS patients (59 and 16 cases respectively) as compared to healthy cohort (34). In Stage I we utilized high-throughput protein arrays (23 232 total signals, in duplicate) to identify proteins of high-interest. In Stage II we designed new protein arrays (352 total signals, in duplicate) to further focus on 25 of the proteins from Stage I and expanded to a larger cohort, including both male and female samples (161 MDS and 43 AML patients; 112 healthy controls). Stage I resulted in 35 proteins displaying increased IgG reactivity in patients as compared to the healthy controls (P< 4.3 x10-07, Bonferroni Corrected P<0.01). This protein subset included 14 proteins associated with cancer, 12 with apoptosis, and 3 with the NFAT Regulation canonical pathway. Using the focused arrays we performed a classification of MDS patients and healthy controls. Stage II subsequently identified a high-interest focused set of 3 proteins, namely AKT3, FCGR3A and ARL8B displaying aberrant increased reactivity in patient subgroups, in concordance with Stage I. Autoantibody reactivity against specific proteins provides complementary information to other known molecular signatures for MDS and may enhance our capabilities for detecting and classifying MDS. In the study presented here, MDS patients were classified into Stable, Transforming or AML post MDS (L) classes retrospectively. The different patients were compared to a healthy cohort to assess increased autoantibody reactivity to specific patients as opposed to healthy groups Stage 2 of study: 633 Files analyzed for: 316 Patients in duplicate and a negative control. The proteins on the array were selected following a first stage using ProtoArrays

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