Class prediction models of thrombocytosis using genetic biomarkers
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE12295 | GEO | 2010/04/11
SECONDARY ACCESSION(S): PRJNA113589
REPOSITORIES: GEO
Similar Datasets
Project description:Using custom spotted oligonucelotide platelet-focused arrays, platelet samples were compared. 48 health controls, 23 reactive thrombocytosis (RT) and 24 essential thrombocythemia (ET) samples were compared. An 11-biomarker gene subset was identified that discriminated among the three cohorts with 86.3% accuracy. 70 mer oligonucleotides were spotted in quadruplicate and hybridized versus reference RNA in two color method. Spiked control RNAs were also included.
2010-04-11 | E-GEOD-12295 | biostudies-arrayexpress
Project description:Post-transcriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biological processes and disease. We systematically dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and healthy controls, and integrated these data with transcriptomic and proteomic platforms. We identified and validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a discrete 3-member subset effectively defines ET phenotypes. The genetic signature includes functional guide and passenger strands of the previously-uncharacterized miR 490 (5p and 3p), both of which displayed restricted, low-level expression in megakaryocytes/platelets (compared to leukocytes), and aberrant expression during thrombocytosis, most profound in essential thrombocythemia (ET). Overexpression of miR 490 in a bilineage differentiation model of megakaryocyte/erythroid progenitor formation was insufficient for hematopoietic stem cell colony differentiation and/or lineage specification. Systematic integration of transcriptomic and mass spectrometric datasets with functional reporter assays identified dishevelled associated activator of morphogenesis 1 (DAAM1) as a unique miR 490 5p protein target demonstrating decreased expression in ET platelets, putatively modulated by translational control (and not by mRNA target degradation). Our data define a dysregulated miRNA fingerprint in thrombocytosis, and collectively support a developmentally-restricted function of miR 490 (and its putative DAAM1 target) to conditions associated with exaggerated megakaryocytopoiesis and/or proplatelet formation. Human platelets from a total of 79 samples in 3 phenotypic groups: essential thrombocythemia (ET, N =27), reactive thrombocytosis (RT, N=22) and healthy controls (NO, N=30) were measured on array platform
2012-11-06 | E-GEOD-39046 | biostudies-arrayexpress
Project description:Post-transcriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biological processes and disease. We systematically dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and healthy controls, and integrated these data with transcriptomic and proteomic platforms. We identified and validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a discrete 3-member subset effectively defines ET phenotypes. The genetic signature includes functional guide and passenger strands of the previously-uncharacterized miR 490 (5p and 3p), both of which displayed restricted, low-level expression in megakaryocytes/platelets (compared to leukocytes), and aberrant expression during thrombocytosis, most profound in essential thrombocythemia (ET). Overexpression of miR 490 in a bilineage differentiation model of megakaryocyte/erythroid progenitor formation was insufficient for hematopoietic stem cell colony differentiation and/or lineage specification. Systematic integration of transcriptomic and mass spectrometric datasets with functional reporter assays identified dishevelled associated activator of morphogenesis 1 (DAAM1) as a unique miR 490 5p protein target demonstrating decreased expression in ET platelets, putatively modulated by translational control (and not by mRNA target degradation). Our data define a dysregulated miRNA fingerprint in thrombocytosis, and collectively support a developmentally-restricted function of miR 490 (and its putative DAAM1 target) to conditions associated with exaggerated megakaryocytopoiesis and/or proplatelet formation.
2012-11-06 | GSE39046 | GEO
Project description:Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia-negative myeloproliferative neoplasms (MPNs) characterized by erythrocytosis and thrombocytosis, respectively. Approximately 95% of PV and 50–70% of ET patients harbour the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET patients carry CALRins5 or CALRdel52 mutations. These ET CARL-mutated subjects show higher platelet count and lower thrombotic risk compared to JAK2-mutated patients. Here we showed that CALR-mutated and JAK2V617F-positive CD34+ cells have different gene and miRNA expression profiles. Indeed, we highlighted several pathways differentially activated between JAK2V617F- and CALR-mutated progenitors, i.e. mTOR, MAPK/PI3K and MYC pathways. Furthermore, we unveiled that the expression of several genes involved in DNA repair, chromatin remodelling, splicing and chromatid cohesion are decreased in CALR-mutated cells. According to the low risk of thrombosis in CALR-mutated patients, we also found the down-regulation of several genes involved in thrombin signalling and platelet activation. As a whole, these data support the model in which CALR-mutated ET could be considered as a distinct disease entity from JAK2V617F-positive MPNs and may provide the molecular basis supporting the different clinical features of these patients.
2018-03-01 | GSE103238 | GEO
Project description:Polycythemia vera (PV) and essential thrombocythemia (ET) are Philadelphia-negative myeloproliferative neoplasms (MPNs) characterized by erythrocytosis and thrombocytosis, respectively. Approximately 95% of PV and 50–70% of ET patients harbour the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET patients carry CALRins5 or CALRdel52 mutations. These ET CARL-mutated subjects show higher platelet count and lower thrombotic risk compared to JAK2-mutated patients. Here we showed that CALR-mutated and JAK2V617F-positive CD34+ cells have different gene and miRNA expression profiles. Indeed, we highlighted several pathways differentially activated between JAK2V617F- and CALR-mutated progenitors, i.e. mTOR, MAPK/PI3K and MYC pathways. Furthermore, we unveiled that the expression of several genes involved in DNA repair, chromatin remodelling, splicing and chromatid cohesion are decreased in CALR-mutated cells. According to the low risk of thrombosis in CALR-mutated patients, we also found the down-regulation of several genes involved in thrombin signalling and platelet activation. As a whole, these data support the model in which CALR-mutated ET could be considered as a distinct disease entity from JAK2V617F-positive MPNs and may provide the molecular basis supporting the different clinical features of these patients.
2018-03-01 | GSE103237 | GEO
Project description:Platelets from patients with myeloproliferative neoplasms (MPNs) exhibit a hyperreactive phenotype. Here, we performed a single cell RNA-seq analysis of primary PBMC samples from essential Thrombocythemia (ET) and healthy individuals (HI) and found significant enrichment of transcripts related to platelet activation, mTOR and oxidative phosphorylation (OXPHOS) in ET platelets.
2024-01-01 | GSE244589 | GEO
Project description:Platelets play an important role in tumor growth and at the same time, platelet characteristics are affected by cancer presence. Therefore, we investigated whether the platelet proteome can be used as a source for biomarkers of early-stage cancer. Patients with early-stage lung (n=8) and head of pancreas cancer (n=4) were included, as were healthy sex- and age-matched controls for each subgroup. Blood samples were collected from controls and from patients before surgery. Furthermore, from six of the patients, a second sample was collected two months after surgery. NanoLC-MS/MS-based proteomics was used to quantify and compare the platelet proteome of patients to controls. Also, samples before surgery and after surgery were compared. Analysis revealed that the platelet proteome of patients with early-stage cancer is altered as compared to controls. In addition, the platelet proteome changed after tumor resection. Using the above data, in conjunction with quantitative filtering, we were able to select seven potential platelet-derived biomarkers of early-stage cancer. This pioneering study on the platelet proteome in cancer patients clearly identifies platelets as a new source of protein biomarkers of early-stage cancer.
2018-08-29 | MSV000082867 | MassIVE
Project description:Platelets play an important role in tumor growth and at the same time, platelet characteristics are affected by cancer presence. Therefore, we investigated whether the platelet proteome can be used as a source for biomarkers of early-stage cancer. Patients with early-stage lung (n=8) and head of pancreas cancer (n=4) were included, as were healthy sex- and age-matched controls for each subgroup. Blood samples were collected from controls and from patients before surgery. Furthermore, from six of the patients, a second sample was collected two months after surgery. NanoLC-MS/MS-based proteomics was used to quantify and compare the platelet proteome of patients to controls. Also, samples before surgery and after surgery were compared. Analysis revealed that the platelet proteome of patients with early-stage cancer is altered as compared to controls. In addition, the platelet proteome changed after tumor resection. Using the above data, in conjunction with quantitative filtering, we were able to select seven potential platelet-derived biomarkers of early-stage cancer. This pioneering study on the platelet proteome in cancer patients clearly identifies platelets as a new source of protein biomarkers of early-stage cancer.
2018-03-09 | PXD005921 | Pride
Project description:Criteria for distinguishing among etiologies of thrombocytosis are limited in their capacity to delineate clonal (essential thrombocythemia [ET]) from nonclonal (reactive thrombocytosis [RT]) etiologies. We studied platelet transcript profiles of 126 subjects (48 controls, 38 RT, 40 ET [24 contained the JAK2V(617)F mutation]) to identify transcript subsets that segregated phenotypes. Cross-platform consistency was validated using quantitative real-time polymerase chain reaction (RT-PCR). Class prediction algorithms were developed to assign phenotypic class between the thrombocytosis cohorts, and by JAK2 genotype. Sex differences were rare in normal and ET cohorts (< 1% of genes) but were male-skewed for approximately 3% of RT genes. An 11-biomarker gene subset using the microarray data discriminated among the 3 cohorts with 86.3% accuracy, with 93.6% accuracy in 2-way class prediction (ET vs RT). Subsequent quantitative RT-PCR analysis established that these biomarkers were 87.1% accurate in prospective classification of a new cohort. A 4-biomarker gene subset predicted JAK2 wild-type ET in more than 85% patient samples using either microarray or RT-PCR profiling, with lower predictive capacity in JAK2V(617)F mutant ET patients. These results establish that distinct genetic biomarker subsets can predict thrombocytosis class using routine phlebotomy.
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Project description:Functional heterogeneity of hematopoietic stem cells (HSCs) heterogeneity has been extensively described in mice, but so far not described in human bone marrow (BM). In particular, HSCs biased towards platelet formation have been identified, and shown to be expanded during ageing and implicated as cells-of-origin for essential thrombocythemia (ET). By combining xenografting of molecularly barcoded adult human BM HSCs and high-throughput single cell RNA sequencing we here identify human BM HSCs that are molecularly and functionally platelet-biased. Furthermore, a quantitative comparison of transcriptomes from young and aged BM HSCs showed that both the proportion of platelet-biased HSCs and their level of molecular platelet priming increases with age.
2024-08-23 | GSE188889 | GEO