No abstract

Congenital Erythrocytosis (CE), also called congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. 3Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and generally results from mutations in the erythropoietin-receptor gene (EPOR).Secondary congenital erythrocytosis arises from conditions which cause tissue hypoxia thus resulting in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (genes HBB, HBA1 and HBA2), decreased production of 2,3-biphosphoglycerate due to mutations in the BPGM gene, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1 and EGLN1). Depending on the affected gene CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo.Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients.With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive internet-based database focusing on the registration of clinical history, hematological, biochemical and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database (LOVD).

A wealth of evidence correlates the chemopreventive activity of a fiber-rich diet with the production of butyrate. In order to identify the genes transcriptionally modulated by the molecule, we analyzed the expression profile of butyrate-treated colon cancer cells by means of cDNA expression arrays. Moreover, the effect of trichostatin A, a specific histone deacetylase inhibitor, was studied. A superimposable group of 23 genes out of 588 investigated is modulated by both butyrate and trichostatin A. Among them, a major target was tob-1, a gene involved in the control of cell cycle. tob-1 is also upregulated by butyrate in a neuroblastoma-derived cell line, and its overexpression in the colon cells caused growth arrest. Our findings represent an extensive analysis of genes modulated by butyrate and identify completely new effectors of its biological activities. ß 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.