30e3f2fc-7a50-4fef-b9be-7e23da44e3d3 - samples
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ABSTRACT:
PROVIDER: EGAD00001007531 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) and seconday myelofibrosis (SMF), comprising post-ET-MF(pET-MF) and post-PV-MF(pPV-MF). In this dataset, we compare the gene expression data of bone marrow or peripheral blood mononuclear cells (BMMCs/PBMCs) of CD34+ cells from MPN patients and healthy donors.
2021-11-24 | GSE174060 | GEO
Project description:An increased number of circulating CD34+ hematopoietic progenitors (HP) and a prominent amplification of dystrophic megakaryocytes (MK) are observed in PMF patients. As transcriptome data from CD34+ hematopoietic progenitors showed modulations of FLT3 and MAP kinase expression independently of the JAK2V617F mutation status Transcriptome analysis was performed on circulating CD34+ cells from PMF patients using Agilent 22K microarray and compared to CD34+ cells from blood and bone marrow from un-mobilized healthy donors. Indirect map: each tested sample was hybridzed with reference probe
2008-07-29 | E-GEOD-12234 | biostudies-arrayexpress
Project description:The comparative characterization of hematopoietic stem cells from healthy stem cell donors and patients with acute myeloid leukemia on a proteome level has the potential to reveal differentially regulated proteins which might be candidates for specific immunotherapy target molecules. Exemplarily, we analyzed the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia employing mass spectrometry. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy stem cell donors were analyzed. In this TMT 10-plex labeling based approach 2068 proteins were identified with 256 proteins differentially regulated in one or both cellular compartments. This study demonstrates the feasibility of a mass spectrometry based proteomic approach to detect differentially expressed proteins in two compartment fractions of leukemic stem cells as compared to their healthy stem cell counterparts.
2018-02-19 | PXD008378 | Pride
Project description:Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of primary myelofibrosis (PMF), polycythemia vera (PV), essential thrombocythemia (ET) and seconday myelofibrosis (pPV-MF or pET-MF) In this dataset, we compare the gene expression data of bone marrow (BM) or peripheral blood (PB) mononuclear cells of CD34+ cells from JAK2V617F mutated patients vs. healthy donors
2022-08-26 | GSE136335 | GEO
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. three NrasG12D/G12D HSCs samples, three NrasG12D/+ HSCs samples, two Nras+/+ HSCs control samples.
2013-05-29 | E-GEOD-46948 | biostudies-arrayexpress
Project description:Genomic studies in chronic myeloid malignancies, including myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS) and MPN/MDS, have identified common mutations in genes encoding signaling, epigenetic, transcription and splicing factors. Analysis of 18 of these genes in a cohort of 224 chronic myelomonocytic leukemias (CMML), which is the most frequent MPN/MDS, identified at least one mutated gene in 95% of the patients, with some of the mutations affecting the disease phenotype. The number of mutated genes negatively affected progression-free and overall survival in multivariate analysis. Analysis of sorted progenitors indicated an early amplification of the CMML clone at the CD34+/CD38- stage of hematopoiesis, together with a premature granulomonocytic differentiation skewing. We interrogated the clone architecture by mutation-specific discrimination analysis of single-cell-derived colonies. The genetic classification of individual colonies allowed a designation of sub-clones and the assembly of putative evolutionary trees, indicating a linear acquisition of the studied mutations. Analysis of matched pre- and post-treatment samples demonstrated clonal persistence with limited and selective elimination of sub-clones. The disease was characterized by an amplification of multipotent and common myeloid progenitors in the CD34+ compartment, both fractions showing increased granulomonocytic differentiation at the expense of erythroid progenitors, contrasting with normal granulomonocytic progenitors. Altogether, early amplification of the leukemic clone and increased granulomonocytic differentiation of early progenitors may account for the specificity of CMML among myeloid neoplasms. This experiment correspond to the analysis of gene expression profiles in total CD34+ cells from the peripheral blood of 15 patients (Chronic Myelomonocytic Leukemia) and 4 healthy controls.
2013-01-17 | E-MTAB-1044 | biostudies-arrayexpress
Project description:Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm whose severity and treatment complexity is attributed to the presence of bone marrow (BM) fibrosis and alterations of stroma impairing the production of normal blood cells. Despite the recently discovered mutations including the JAK2V617F mutation in about half of patients, the primitive event responsible for the clonal proliferation is still unknown. In the highly inflammatory context of PMF, the presence of fibrosis associated with a neoangiogenesis and an osteosclerosis concomitant to the myeloproliferation and to the increase number of circulating hematopoietic progenitors suggests that the crosstalk between hematopoietic and stromal cells is deregulated in the PMF BM microenvironment. Within these niches, Mesenchymal Stromal Cells (BM-MSC) play a supportive role in the production of growth factors and extracellular matrix which regulate the proliferation, differentiation, adhesion and migration of hematopoietic progenitors. A transcriptome analysis of BM-MSC in PMF patients will help to characterize their molecular alterations and to understand their involvement in the hematopoietic progenitor deregulation that features PMF. Primary Myelofibrosis, mesenchymal stroma cells, bone marrow, myeloproliferative disorders Transcriptome analysis was performed on BM-MSC amplified in vitro after 3 to 5 passages. Agilent Whole Human Genome Oligo Microarrays were used to compare expression profiling of BM-MSC from PMF patients and healthy donors.
2015-01-10 | E-GEOD-44426 | biostudies-arrayexpress
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis.
2013-05-29 | GSE46948 | GEO
Project description:Ph-negative myeloproliferative neoplasms (MPNs) are characterized by many somatic mutations which have already been shown useful in the prognostic assessment of MPN patients. Moreover, aberrant microRNA (miRNA) expression seems to add to the molecular complexity of MPNs, as specific miRNA signatures capable of discriminating MPN cells from those of normal donors were previously reported. In order to have a comprehensive picture of miRNA deregulation and its relationship with differential gene expression in primary myelofibrosis (PMF) cells, we obtained gene- (GEP) and miRNA expression profiles (miEP) of CD34+ cells from 31 healthy donors and 42 PMF patients using Affymetrix technology (HG-U219 and miRNA 2.0 arrays). Differentially expressed genes (DEG) and miRNAs (DEM) were sorted out by means of Partek Genomic Suite vs 6.6. Since each miRNA can target many mRNAs while a single mRNA can be targeted by multiple miRNAs, we performed Integrative Analysis (IA) by means of Ingenuity Pathway Analysis (IPA) to untangle this combinatorial complexity. In particular, IPA points out DEM-DEG pairs among experimentally validated interactions from TarBase, miRecords and Ingenuity Expert Findings as well as predicted microRNA-mRNA interactions from TargetScan. IPA microRNA Target Filter was then employed to select only the DEM-DEG pairs showing an anti-correlated expression pattern and to build regulatory networks. Finally, 3'UTR luciferase reporter assays were performed to validate IPA predicted miRNA-mRNA interactions. This study allowed the identification of different networks possibly involved in PMF onset and progression, highlighting an aberrant cross-regulation in miRNA-targets involved in malignant hematopoiesis. Furthermore, Integrative analysis was proved a powerful tool to unravel miRNA-mRNA interactions in functional networks, shedding light on the potential contribution of miRNAs to PMF pathogenesis. Gene expression profile (GEP) and miRNA expression profile (miEP) were performed starting from the same totalRNA of CD34+ cells from 42 PMF patients and 31 healthy donors (n=16 PB CD34+, n=15 BM CD34+) (1 replicate for each sample). In particular, GEP and miEP were performed on 23 PMF patients carrying the mutation JAK2V617F and 19 wild-type samples.
2014-10-01 | E-GEOD-53482 | biostudies-arrayexpress
Project description:In this study, we explored the transcriptome of hematopoietic stem cells (HSCs) and megakaryocyte-erythroid progenitors (MEPs) in JAK2 V617F+ PV and ET and found that distinctive gene expression patterns within MPN subtypes begin at the HSC stage. HSCs from ET exhibited prominent megakaryocyte (Mk)-lineage priming. The differentially expressed genes (DEGs) indicated that cellular processes and signaling pathways in HSCs and MEPs from healthy donors (HDs), PV and ET patients are differentially modulated
2021-02-22 | GSE111410 | GEO