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Blood, 1 August 2008, Vol. 112, No. 3, pp. 568-575. Prepublished online as a Blood First Edition Paper on June 3, 2008; DOI 10.1182/blood-2007-10-118331. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2007-10-118331v1 112/3/568    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Taussig, D. C. Articles by Bonnet, D. Search for Related Content PubMed PubMed Citation Articles by Taussig, D. C. Articles by Bonnet, D. Related Collections Hematopoiesis and Stem Cells Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Anti-CD38 antibody–mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells David C. Taussig1,2, Farideh Miraki-Moud1,*, Fernando Anjos-Afonso2,*, Daniel J. Pearce2, Kirsty Allen3, Christopher Ridler2, Debra Lillington1, Heather Oakervee1, Jamie Cavenagh1, Samir G. Agrawal1, T. Andrew Lister1, John G. Gribben1, and Dominique Bonnet2 1 Department of Medical Oncology, St Bartholomew's Hospital, London; and 2 Haematopoietic Stem Cell Laboratory and 3 FACS Laboratory, Cancer Research United Kingdom London Research Institute, London, United Kingdom Immunodeficient mice are increasingly used to assay human hematopoietic repopulating cells as well as leukemia-initiating cells. One method commonly used to isolate these rare cells is to sort cells stained with fluorochrome-conjugated antibodies into fractions, then transplant the different fractions into immunodeficient mice to test their repopulating ability. The antibodies are generally treated as being neutral in terms of their effects on the experiment. Human repopulating cells are thought to express CD34 and lack CD38. Here we present evidence that anti-CD38 antibodies have a profound inhibitory effect on engraftment of cord blood and leukemia cells. We show that this effect is Fc-mediated and can be overcome by treating mice with immunosuppressive antibodies. When this inhibitory effect is prevented, we demonstrate that the CD34+CD38+ fraction of certain acute myeloid leukemia samples contains all, or at least most, leukemia-initiating cell capacity. This study highlights the potential pitfall of antibody-mediated clearance of repopulating cells and is important for any groups working with this model. More importantly, the work suggests that there is greater variation in the phenotypes of leukemia-initiating cells than previously suggested. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. van der Weide, S. D.P.W.M. de Jonge-Peeters, F. Kuipers, E. G.E. de Vries, and E. Vellenga Combining Simvastatin with the Farnesyltransferase Inhibitor Tipifarnib Results in an Enhanced Cytotoxic Effect in a Subset of Primary CD34+ Acute Myeloid Leukemia Samples Clin. Cancer Res., May 1, 2009; 15(9): 3076 - 3083. [Abstract] [Full Text] [PDF] O. Heidenreich and J. Vormoor Malignant stem cells in childhood ALL: the debate continues! Blood, April 30, 2009; 113(18): 4476 - 4477. [Full Text] [PDF] C. V. Cox, P. Diamanti, R. S. Evely, P. R. Kearns, and A. Blair Expression of CD133 on leukemia-initiating cells in childhood ALL Blood, April 2, 2009; 113(14): 3287 - 3296. [Abstract] [Full Text] [PDF]

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