SEARCH:   Advanced

Blood, 15 March 2006, Vol. 107, No. 6, pp. 2219-2222. Prepublished online as a Blood First Edition Paper on November 10, 2005; DOI 10.1182/blood-2005-08-3429. This Article Full Text (PDF) All Versions of this Article: 2005-08-3429v1 107/6/2219    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Burkitt, M. J Articles by Raafat, A. Search for Related Content PubMed PubMed Citation Articles by Burkitt, M. J Articles by Raafat, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 24, 2005 Accepted October 26, 2005 Nitric oxide generation from hydroxyurea: significance and implications for leukemogenesis in the management of myeloproliferative disorders Mark J Burkitt* and Alaeddin Raafat Gray Cancer Institute, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom Department of Haematology, Monklands Hospital, Airdrie, Lanarkshire, United Kingdom * Corresponding author; email: burkitt{at}gci.ac.uk. The use of myelosuppressive agents to reduce the risk of thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET) has been associated with an increased risk of transformation to acute myeloid leukemia (AML). Whereas chlorambucil, busulfan and radiophosphorus (32P) have been demonstrated to increase the risk of transformation, the leukemogenic potential of hydroxyurea (HU) continues to be a matter of debate. Clinical studies have suggested that HU may cause a small increase in the risk of AML, but it has proven difficult to establish whether AML is actually caused by HU or arises during the natural progression of PV and ET. Reports that HU undergoes metabolic activation to species that induce mutation appear to support the notion that it is leukemogenic. In this Perspectives article, we suggest that the ability of HU to induce mutation in cell culture studies results from the generation of nitrogen dioxide via the autoxidation of nitric oxide, a product of HU metabolism. However, we argue that autoxidation would not occur in vivo, leading to the conclusion that generation of the mutagen nitrogen dioxide is peculiar to cell culture systems and has little relevance to the use of HU in the management of PV and ET. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Martinez-Rojano, J. Mancilla-Ramirez, L. Quinonez-Diaz, and N. Galindo-Sevilla Activity of Hydroxyurea against Leishmania mexicana Antimicrob. Agents Chemother., October 1, 2008; 52(10): 3642 - 3647. [Abstract] [Full Text] [PDF] V. P. Cokic, B. B. Beleslin-Cokic, M. Tomic, S. S. Stojilkovic, C. T. Noguchi, and A. N. Schechter Hydroxyurea induces the eNOS-cGMP pathway in endothelial cells Blood, July 1, 2006; 108(1): 184 - 191. [Abstract] [Full Text] [PDF]

	Copyright © 2005 by American Society of Hematology         Online ISSN: 1528-0020