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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3743-3745. Prepublished online as a Blood First Edition Paper on January 4, 2005; DOI 10.1182/blood-2004-07-2949. This Article Full Text (PDF) All Versions of this Article: 2004-07-2949v1 105/9/3743    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Larghero, J. Articles by Rousselot, P. Search for Related Content PubMed PubMed Citation Articles by Larghero, J. Articles by Rousselot, P. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 30, 2004 Accepted December 30, 2004 Farnesyltransferase inhibitor tipifarnib (ZarnestraTM, R115777) preferentially inhibits in vitro autonomous erythropoiesis of polycythemia vera patient cells Jerome Larghero, Nathalie Gervais, Bruno Cassinat, Jean-Didier Rain, Marie-Helene Schlageter, Rose Ann Padua, Christine Chomienne, and Philippe Rousselot* Laboratoire de Biologie Cellulaire Hematopoietique EMI00-03, Institut d'Hematologie and Service de Medecine Nucleaire, Hopital Saint-Louis, Paris, France; Unite de Therapie Cellulaire, Hopital Saint-Louis, Paris, France Laboratoire de Biologie Cellulaire Hematopoietique EMI00-03, Institut d'Hematologie and Service de Medecine Nucleaire, Hopital Saint-Louis, Paris, France Laboratoire de Biologie Cellulaire Hematopoietique EMI00-03, Institut d'Hematologie and Service de Medecine Nucleaire, Hopital Saint-Louis, Paris, France; Service Clinique des Maladies du Sang, Hopital Saint-Louis, Paris, France * Corresponding author; email: philippe.rousselot{at}chu-stlouis.fr. Polycythemia vera (PV) is an acquired myeloproliferative disorder with primary expansion of the red cell mass leading to an increased risk of thrombosis and less frequently to myelofibrosis and secondary acute leukemia. Standard therapies include cytoreduction with either phlebotomy and chemotherapeutic agents and antithrombotic drugs. Because long term exposure to cytotoxic chemotherapy may increase the risk of acute transformation, new therapeutic options are needed. Tipifarnib is a non-peptidomimetic inhibitor of farnesyl transferase that was developed as a potential inhibitor of RAS signalling. In the present study we report that tipifarnib used at pharmacologically achievable concentrations strongly inhibits the BFU-E autonomous growth which characterizes PV patients. Moreover at low tipifarnib concentrations (0.15 µM), the inhibitory effect was preferentially observed in PV BFU-E progenitors and not in normal BFU-E progenitors and was not rescued by EPO. Thus tipifarmib may specifically target PV stem cells and may be of clinical interest in the treatment of PV patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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