Dataset Information

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

ABSTRACT: Posttranscriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biologic processes. We dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and controls, and integrated data with transcriptomic and proteomic platforms. We validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a 3-member subset defines essential thrombocythemia (ET). The genetic signature includes functional guide and passenger strands of the previously uncharacterized miR 490 (5p and 3p), which displayed restricted, low-level expression in megakaryocytes/platelets (compared with leukocytes), and aberrant expression during thrombocytosis, most profound in ET. Overexpression of miR 490 in a bilineage differentiation model of megakaryocyte/erythroid progenitor formation was insufficient for hematopoietic colony differentiation and/or lineage specification. Integration of transcriptomic and mass spectrometric datasets with functional reporter assays identified dishevelled associated activator of morphogenesis 1 (DAAM1) as a miR 490 5p protein target demonstrating decreased expression in ET platelets, putatively by translational control (and not by mRNA target degradation). Our data define a dysregulated miRNA fingerprint in thrombocytosis and support a developmentally restricted function of miR 490 (and its putative DAAM1 target) to conditions associated with exaggerated megakaryocytopoiesis and/or proplatelet formation.

SUBMITTER: Xu X

PROVIDER: S-EPMC3482865 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

Xu Xiao X Gnatenko Dmitri V DV Ju Jingfang J Hitchcock Ian S IS Martin Dwight W DW Zhu Wei W Bahou Wadie F WF

Blood 20120806 17

Posttranscriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biologic processes. We dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and controls, and integrated data with transcriptomic and proteomic platforms. We validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a 3-member subset defines essential th ...[more]

PMID: 22869791

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Project description:The purpose of this study was to provide a more precise definition of an integrated oncogeriatric approach (IOGA) through concept analysis. The literature was reviewed from January 2005 to April 2011 integrating three broad terms: geriatric oncology, multidisciplinarity and integrated care delivery models. Citation selection was based on: (1) elderly cancer patients as the study population; (2) disease management and (3) case studies, intervention studies, assessments, evaluations and studies. Inclusion and exclusion criteria were refined in the course of the literature search. Initiatives in geriatric oncology that relate to oncology services, social support services and primary care services for elderly cancer patients. Elderly cancer patients aged 70 years old or more. Rodgers' concept analysis method was used for this study. The analysis was carried out according to thematic analysis based on the elements of the Chronic Care Model. The search identified 618 citations. After in-depth appraisal of 327 potential citations, 62 articles that met our inclusion criteria were included in the analysis. Three IOGA main attributes were identified, which constitute IOGA's core aspects: geriatric assessment (GA), comorbidity burden and treatment outcomes. The IOGA concept comprises two broad antecedents: coordinated healthcare delivery and primary supportive care services. Regarding the consequents of an integrated approach in geriatric oncology, the studies reviewed remain inconclusive. Our study highlights the pioneering character of the multidimensional IOGA concept, for which the relationship between clinical and organisational attributes, on the one hand, and contextual antecedents, on the other, is not well understood. We have yet to ascertain IOGA's consequents. IMPLICATIONS OF KEY FINDINGS: There is clearly a need for a whole-system approach to change that will provide direction for multilevel (clinical, organisational, strategic) interventions to support interdisciplinary practice, education and research.

Dataset Information

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

Publications

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

Similar Datasets

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