Distinct Transcriptomic and Exomic Abnormalities within Myelodysplastic Syndrome Marrow Cells
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ABSTRACT:
PROVIDER: PRJNA435879 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6781180_1.fastq.gz | Fastqsanger.gz | |||
| SRR6781180_2.fastq.gz | Fastqsanger.gz | |||
| SRR6781190_1.fastq.gz | Fastqsanger.gz | |||
| SRR6781190_2.fastq.gz | Fastqsanger.gz | |||
| SRR6781200_1.fastq.gz | Fastqsanger.gz |
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Project description:Prior studies using DNA microarray platforms have shown alterations of gene expression profiles (GEPs) of marrow cells in myelodysplastic syndromes (MDS). Using the increased sensitivity and accuracy of high-throughput RNA sequencing (RNA-Seq) for detecting and quantifying mRNA transcripts, our study has demonstrated novel significant differences in GEPs between MDS and normal CD34+ marrow cells with 41 genes identified as disease classifiers. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable (sMDS) vs patients whose illness transformed to acute myeloid leukemia within 12 months (tMDS). The genes whose expression was associated with disease outcome were involved in functional pathways and biologic processes highly relevant for MDS. Exomic analysis identified MDS-associated pathogenic mutations in virtually all patients tested. MDS subgroups with spliceosome mutations demonstrated distinct differential isoform usage and expression and consequent dysregulation of distinct biological functions. This combination of clinical, transcriptomic and exomic findings provides valuable molecular insights into the mechanisms underlying MDS and its progression to a more aggressive stage and also facilitates prognostic characterization of MDS patients.
2018-04-09 | GSE111085 | GEO
Project description:To provide biologic insights into mechanisms underlying myelodysplastic syndromes (MDS) we evaluated the CD34+ marrow cells transcriptome using high-throughput RNA sequencing (RNA-Seq). We demonstrated significant differential gene expression profiles (GEPs) between MDS and normal and identified 41 disease classifier genes. Additionally, two main clusters of GEPs distinguished patients based on their major clinical features, particularly between those whose disease remained stable versus patients who transformed into acute myeloid leukemia within 12 months. The genes whose expression was associated with disease outcome were involved in functional pathways and biologic processes highly relevant for MDS. Combined with exomic analysis we identified differential isoform usage of genes in MDS mutational subgroups, with consequent dysregulation of distinct biologic functions. This combination of clinical, transcriptomic and exomic findings provides valuable understanding of mechanisms underlying MDS and its progression to a more aggressive stage and also facilitates prognostic characterization of MDS patients.
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Project description:Diamond Blackfan anemia is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, often with associated physical abnormalities. Perturbations of the ribosome appear critically important to the development of DBA, as alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, presently only 50-60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide SNP array to evaluate for regions of recurrent copy variation, we identified 2 patients with mosaic loss in the region of the the chromosome 5-deleted region involved in somatically-acquired 5q- myelodysplastic syndrome.
2013-11-05 | GSE42570 | GEO
Project description:Diamond Blackfan anemia is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, often with associated physical abnormalities. Perturbations of the ribosome appear critically important to the development of DBA, as alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, presently only 50-60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide SNP array to evaluate for regions of recurrent copy variation, we identified 2 patients with mosaic loss in the region of the the chromosome 5-deleted region involved in somatically-acquired 5q- myelodysplastic syndrome. Samples were analyzed on Illumina HumanOmni1_Quad, HumanOmniExpress, or HumanOmniExpressExome Genotyping bead arrays; 1 patient was available for longitudinal study including assessment of mosaicism in lymphoid and myeloid-enriched cell populations before treatement with lenolidamide. Similar studies were performed while on lenoldamide therapy in peripheral blood at 3 months and in bone marrow at 20 months of treatment. One patient with mosaic deletion of 5q was available for longitudinal study including assessment of gene expression in bone marrow before and during treatment with lenalidomide.
2013-11-05 | E-GEOD-42570 | biostudies-arrayexpress
Project description:Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell diseases characterized by dysplasia of one or more hematologic lineages and a high-risk of developing acute myeloid leukemia (AML). MDS patients have recurrent bacterial infections and abnormal expression of CD56 by monocytes. We investigated MDS patients’ bone marrow CD56+/CD56- monocytes and their in vitro derived dendritic cell (DCs) populations in comparison to cells obtained from disease-free subjects. We found that monocytes from MDS patients, irrespective of CD56 expression, have reduced phagocytosis activity and low expression of genes involved in triggering immune responses, regulation of immune and inflammatory response signaling pathways, and in the response to lipopolysaccharide. Dendritic cells (DCs) derived in vitro from MDS monocytes failed to develop dendritic projections and had reduced expression of HLA-DR and CD86 suggesting that antigen processing and T cell activation capabilities are impaired. In conclusion, we identified in both CD56+ and CD56- monocytes from MDS-patients several abnormalities that may be related to the increased susceptibility to infections observed in these patients.
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Project description:Analysis of musashi2 contribution towards maintaing myelodysplastic phenotype in stem cells. We find that musashi2 plays an integral role in maintaining the myelodysplastic phenotype
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Project description:Analysis of Lin-c-Kit+Sca-1- haematopoietic stem cells (HSCs) expressing the Nup98-HoxD13 (NHD13) fusion gene. NHD13 induces myelodysplastic syndrome (MDS) in mice. Results provide insight into the molecular basis of the myelodysplastic phenotype WT mouse HSCs were compared to an NHD13 mutant sequenced in triplicate on a HiSeq 2000
2016-07-03 | E-GEOD-66264 | biostudies-arrayexpress
Project description:Analysis of musashi2 contribution towards maintaing myelodysplastic phenotype in stem cells. We find that musashi2 plays an integral role in maintaining the myelodysplastic phenotype Control, NUP98-HOXD13; NHD13, NHD13/MSI2 bone marrow was transplated allowed to engraft into lethally irradiated congenic CD45.1 animals. Mice were then fed doxycycline to induce MSI2 overexpression. Mice were induced for 3 months and then CD45.2 Lineage lo Sca1+ and Kit+ cells were sorted and then assessed for gene expression.
2016-02-16 | E-GEOD-76840 | biostudies-arrayexpress
Project description:Microarray analysis with 40,000 cDNA gene chip arrays determined differential gene expression profiles (GEPs) in CD34+ marrow cells from myelodysplastic syndrome (MDS) patients compared to normal individuals. Using focused bioinformatics analyses, we found 1175 genes significantly differentially expressed by MDS vs Normal, requiring a minimum of 39 genes to separately classify these patients. Major GEP differences were demonstrated between Normal and MDS patients and between several MDS subgroups: (1) those whose disease remained stable (sMDS) and those who subsequently transformed (tMDS) to acute myeloid leukemia (AML); (2) between del(5q) and other MDS patients. A 6-gene ‘poor risk’ signature was defined which was associated with AML transformation and provided additive prognostic information for IPSS Intermediate-1 patients. Over-expression of genes generating ribosomal proteins and for other signaling pathways was demonstrated in the tMDS patients. Comparison of del(5q) to the remaining MDS patients showed 1924 differentially expressed genes, with under-expression of 1014 genes, 11 of which were within the 5q31-32 Commonly Deleted Region. These data demonstrated (1) GEPs distinguishing MDS patients from normal and between those with differing clinical outcomes (tMDS vs sMDS) and cytogenetics [eg, del(5q)] ; and (2) molecular criteria refining prognostic categorization and associated biologic processes in MDS. Gene expression profiles from CD34+ cells of 35 MDS subjects and 6 Normals were compared.
2009-10-31 | E-GEOD-18366 | biostudies-arrayexpress
Project description:Analysis of Lin-c-Kit+Sca-1- haematopoietic stem cells (HSCs) expressing the Nup98-HoxD13 (NHD13) fusion gene. NHD13 induces myelodysplastic syndrome (MDS) in mice. Results provide insight into the molecular basis of the myelodysplastic phenotype
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