The molecular mechanisms that control thrombopoiesis.

Department of Medicine, Division of Hematology/Oncology, University of California, San Diego, California 92103-3931, USA.
Journal of Clinical Investigation (Impact Factor: 13.77). 01/2006; 115(12):3339-47. DOI: 10.1172/JCI26674
Source: PubMed

ABSTRACT Our understanding of thrombopoiesis--the formation of blood platelets--has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.

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    ABSTRACT: ARTÍCULO DE REVISIÓN han identificado compuestos orgánicos volátiles y metales. Estos últimos son el interés de nuestro grupo de trabajo, en especial el vanadio, elemento liberado a la atmósfera como consecuencia de la quema de combustibles de origen orgá-nico, en especial de los combustibles cuyo origen es el petróleo mexicano, el venezolano o kwaitiano. 1 Este elemento indujo en nuestro modelo animal megaca-riocitosis y trombocitosis. 2-6 El hallazgo nos condujo a iden-tificar los mecanismos por los cuales se producen estas alteraciones, y como consecuencia exploramos las vías normales de señalización que nos permitirán tener un mejor conocimiento de la regulación de este fenómeno, como la producción de megacariocitos y plaquetas.
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    Journal of Clinical and Experimental Investigations. 03/2012;
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    ABSTRACT: Background The incidence of Acute Megakaryoblastic Leukemia (AMKL) is 500-fold higher in children with Down Syndrome (DS) compared with non-DS children, but the relevance of trisomy 21 as a specific background of AMKL in DS is still an open issue. Several Authors have determined gene expression profiles by microarray analysis in DS and/or non-DS AMKL. Due to the rarity of AMKL, these studies were typically limited to a small group of samples.Methods We generated integrated quantitative transcriptome maps by systematic meta-analysis from any available gene expression profile dataset related to AMKL in pediatric age. This task has been accomplished using a tool recently described by us for the generation and the analysis of quantitative transcriptome maps, TRAM (Transcriptome Mapper), which allows effective integration of data obtained from different experimenters, experimental platforms and data sources. This allowed us to explore gene expression changes involved in transition from normal megakaryocytes (MK, n=19) to DS (n=43) or non-DS (n=45) AMKL blasts, including the analysis of Transient Myeloproliferative Disorder (TMD, n=20), a pre-leukemia condition.ResultsWe propose a biological model of the transcriptome depicting progressive changes from MK to TMD and then to DS AMKL. The data indicate the repression of genes involved in MK differentiation, in particular the cluster on chromosome 4 including PF4 (platelet factor 4) and PPBP (pro-platelet basic protein); the gene for the mitogenactivated protein kinase MAPK3K10 and the thrombopoietin receptor gene MPL. Moreover, comparing both DS and non-DS AMKL with MK, we identified three potential clinical markers of progression to AMKL: TMEM241 (transmembrane protein 241) was the most over-expressed single gene, while APOC2 (apolipoprotein C-II) and ZNF587B (zinc finger protein 587B) appear to be the most discriminant markers of progression, specifically to DS AMKL. Finally, the chromosome 21 (chr21) genes resulted to be the most over-expressed in DS and non-DS AMKL, as well as in TMD, pointing out a key role of chr21 genes in differentiating AMKL from MK.Conclusions Our study presents an integrated original model of the DS AMLK transcriptome, providing the identification of genes relevant for its pathophysiology which can potentially be new clinical markers.
    BMC Medical Genomics 12/2014; 7(1):63. · 3.91 Impact Factor


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