Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of telomerase catalytic subunit hTERT in clonal malignancies including human leukemia is fundamental in overcoming cell senescence and enabling prolonged proliferation. One direct transcriptional activator of hTERT is the oncogene MYC which is known to be, in turn, activated by JAK2. To explore the relationship of telomerase, MYC and JAK2 in chronic myeloproliferative diseases, we investigated hTERT and MYC expression in bone marrow cells of essential thrombocythemia (ET) and polycythemia vera (PV). We could determine an up-regulation of MYC expression exclusively in JAK2(wt) ET, whereas hTERT expression was rather inconsistent across the groups. Interestingly, a significant correlation between MYC and hTERT expression could only be established in homozygous JAK2(V617F) PV and control cases. Thus, the functional link between MYC and hTERT seems to be impaired depending on the molecular ET subtype, which in turn may have implications on the phenotype and course of the disease.
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PMID:The expression levels of telomerase catalytic subunit hTERT and oncogenic MYC in essential thrombocythemia are affected by the molecular subtype. 1808 61

Thrombosis is a leading cause of morbidity and mortality in patients with myeloproliferative disorders (MPDs), particularly polycythemia vera (PV) and essential thrombocythemia (ET). Despite the attempts to establish a link between them, the shared biological mechanisms are yet to be characterized. An integrated gene expression meta-analysis of five independent publicly available microarray data of the three diseases was conducted to identify shared gene expression signatures and overlapping biological processes. Using INMEX bioinformatic tool, based on combined Effect Size (ES) approaches, we identified a total of 1,157 differentially expressed genes (DEGs) (697 overexpressed and 460 underexpressed genes) shared between the three diseases. EnrichR tool's rich library was used for comprehensive functional enrichment and pathway analysis which revealed "mRNA Splicing" and "SUMO E3 ligases SUMOylate target proteins" among the most enriched terms. Network based meta-analysis identified MYC and FN1 to be the most highly ranked hub genes. Our results reveal that the alterations in biomarkers of the coagulation cascade like F2R, PROS1, SELPLG and ITGB2 were common between the three diseases. Interestingly, the study has generated a novel database of candidate genetic markers, pathways and transcription factors shared between thrombosis and MPDs, which might aid in the development of prognostic therapeutic biomarkers.
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PMID:Comprehensive Gene expression meta-analysis and integrated bioinformatic approaches reveal shared signatures between thrombosis and myeloproliferative disorders. 2789 26

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 harbor the V617F mutation in the exon 14 of JAK2 gene, while about 20-30% of ET patients carry CALRins5 or CALRdel52 mutations. These ET CALR-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 display 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 remodeling, 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 downregulation of several genes involved in thrombin signaling and platelet activation. As a whole, these data support the model that 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.
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PMID:CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles. 2921 33