Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA262556 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we assessed the effects of lysyl oxidase (LOX/LOXL) inhibition on the composition of extracellular matrix (ECM) produced by in vitro expanded bone marrow derived mesenchymal stromal cells (MSCs) of n=3 patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN).
2023-02-17 | PXD031217 | Pride
Project description:Transcriptome analysis of total RNA from bone marrow (BM) mononuclear cells of MDS patients and normal dornors Global gene expression and alternative splicing profiling among patients with myelodysplastic syndrome (MDS) compared with normal donors
2018-12-05 | GSE107400 | GEO
Project description:Myelodysplastic syndrome (MDS) is a group of heterogeneous clonal stem cell disorders. We hypothesize that gene expression changes in the bone marrow (BM) microenvironment might play a fundamental role in the development and progression of MDS. The goal of the present study is to investigate the differences in gene expression profiles of BM mesenchymal stromal cells (MSCs) between MDS patients and normal individuals, as well as between MDS subtypes. To this end, we applied global gene expression profiling on BM MSCs from adult de novo MDS patients and from controls. The results suggest that gene expression of the MDS BM microenvironment is difference from control BM. In particular, interferon signaling pathway was shown to be up-regulated in MDS BM. The results also showed altered expression according to disease progression. The present study provides evidence supporting MDS as an immune disease and suggests that BM MSCs are a possible therapeutic target in MDS.
2015-03-25 | GSE61853 | GEO
Project description:This study aimed to find the functional circular RNA and further analyze its biological and clinical significance in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients.The circRNAs profiles were analyzed using the Arraystar human circRNA microarray with bone marrow samples from 5 MDS patients, 5 AML patients and 4 controls. Real-time quantitative polymerase chain reaction was carried on circZBTB46 in bone marrow samples from 124 MDS patients, 116 AML patients and 37 controls, and subsequently associated with clinicopathological characteristics and survival of MDS and AML patients.Furthermore, functional studies were conducted by silencing and rescuing/increasing circZBTB46 expression in SKM-1, THP-1 and K562 cell lines. Our results suggested the essential role of circZBTB46 in the progression of MDS and AML, and might be a poor indicator of hematological malignancies.
2020-12-17 | GSE163386 | GEO
Project description:A dosage-dependent role for tumor suppressor genes in the initiation of myeloid malignancies remains controversial. Here we show that MYBL2 is expressed at sharply reduced levels in CD34+ cells from most patients with myelodysplastic syndrome (MDS; 65%; n=26). In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors led to clonal dominance by these M-bM-^@M-^\sub-haploinsufficientM-bM-^@M-^] cells, affecting all blood cell lineages. By 6 months post-transplantation, the reconstituted mice had developed a myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. Thus, downregulation of MYBL2 activity to levels below those predicted by classical haploinsufficiency drives the clonal expansion of hematopoietic progenitors in a large fraction of human MDS cases. Total RNA was prepared from CD34+ bone marrow cells obtained from MDS patients or healthy controls.
2013-09-15 | E-GEOD-43399 | biostudies-arrayexpress
Project description:Altered bone marrow hematopoiesis and immune suppression is a hallmark of myelodysplastic syndrome (MDS). While the bone marrow microenvironment influences malignant hematopoiesis, the mechanism leading to MDS-associated immune suppression is unknown. We tested whether mesenchymal stromal cells (MSCs) contribute to this process. Here, we developed a model to study cultured MSCs from MDS patients compared to similar aged matched normal controls for regulation of immune function. MSCs from MDS patients (MDS-MSC) and healthy donor MSC (HD-MSC) exhibited a similar in vitro phenotype and neither had a direct effect on NK cell function. However, when MDS and HD-MSCs were cultured with monocytes, only the MDS-MSCs acquired phenotypic and metabolic properties of myeloid-derived suppressor cells (MDSCs), with resulting suppression of NK cell function, along with T cell proliferation. A unique MSC transcriptome was observed in MDS-MSCs compared to HD-MSCs, including increased expression of the reactive oxygen species (ROS) regulator, ENC1. High ENC1 expression in MDS-MSC induced suppressive monocytes with increased INHBA, a gene that encodes for a member of the TGF? superfamily of proteins. These monocytes also had reduced expression of the TGF? transcriptional repressor MAB21L2, further adding to their immune suppressive function. Silencing ENC1 or inhibiting ROS production in MDS-MSCs abrogated the suppressive function of MDS-MSC conditioned monocytes. In addition, silencing MAB21L2 in healthy MSC conditioned monocytes mimicked the MDS-MSC suppressive transformation of monocytes. Our data demonstrate that MDS-MSCs are responsible for inducing an immune suppressive microenvironment in MDS through an indirect mechanism involving monocytes.
2020-02-11 | GSE140101 | GEO
Project description:RNA-seq of bone marrow CD34+ cells of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) patients to identify at the molecular pathways involved in primary resistance to AZA therapy.
2017-07-20 | GSE76203 | GEO
Project description:An increasing body of work reveals aberrant hypermethylation of genes occurring in and potentially contributing to the pathogenesis of myeloid malignancies. Several of these diseases, such as myelodysplastic syndromes (MDS), are responsive to DNA methyltransferase inhibitors. In order to determine the extent of promoter hypermethylation in such tumors we compared the distribution of DNA methylation of 14,000 promoters in MDS and secondary AML patients enrolled in a phase I trial of 5-azacytidine and the histone deacetylase inhibitor entinostat against de novo AML patients and normal CD34+ bone marrow cells. The MDS and secondary AML patients displayed more extensive aberrant DNA methylation involving thousands of genes than did the normal CD34+ bone marrow cells or de novo AML blasts. Aberrant methylation in MDS and secondary AML tended to affect particular chromosomal regions, occurred more frequently in Alu poor genes, and included prominent involvement of genes involved in the WNT and MAPK signaling pathways. DNA methylation was also measured at days 15 and 29 after the first treatment cycle. DNA methylation was reversed at day 15 in a uniform manner throughout the genome, and this effect persisted through day 29, even without continuous administration of the study drugs. Keywords: DNA methylation profiling Direct comparison of DNA methylation in bone marrow samples from patients with Myelodysplastic syndrome or secondary Acute Myeloid Leukemia (AML) at baseline and after in vivo treatment with 5-azacytidine + etinostat. A comparison to de novo normal karyotype AML was also performed. Two control groups were included: one consisting of 8 CD34+ bone marrow samples from healthy donors and a second one consisting of matched CD34+ and CD34- fractions from the bone marrows of 4 healthy donors.
2010-05-15 | E-GEOD-17328 | biostudies-arrayexpress
Project description:Epigenome analysis of normal and myelodysplastic sundrome (MDS) bone marrow derived mesenchymal stromal cells (MSCs)
| PRJNA489804 | ENA
Project description:Myelodysplastic syndromes (MDS) are a heterogenous group of diseases affecting the hematopoietic stem cell that are curable only by stem cell transplantation. Both hematopoietic cell intrinsic changes and extrinsic signals from the bone marrow niche seem to ultimately lead to MDS. Animal models of MDS indicate that alterations in specific mesenchymal progenitor subsets in the bone marrow microenvironment can induce or select for abnormal hematopoietic cells. Here we identify a subset of human bone marrow (BM) mesenchymal cells marked by the expression of CD271, CD146 and CD106. This subset of human mesenchymal cells is equivalent to those in mice that, when perturbed, results in an MDS-like syndrome. Transcriptional analysis identified epithelial to mesenchymal transition as the most enriched gene set and Osteopontin (SPP1) as the most overexpressed gene. The loss of expression of Spp1 in the microenvironment resulted in an accelerated progression of the transplanted Vav-driven Nup98-HoxD13 MDS model as demonstrated by increased chimerism, increased contribution of mutant cells to the myeloid lineage and a more pronounced anemia when compared to animals with a wild type microenvironment. These data indicate that molecular perturbations can occur in specific bone marrow mesenchymal subsets of MDS patients. However, the niche adaptations to dysplastic clones include Spp1 overexpression that can constrain disease progression. Therefore, niche changes with malignant disease can also serve to protect the host.
2023-08-31 | GSE212638 | GEO