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Prepublished online as a Blood First Edition Paper on December 27, 2002; DOI 10.1182/blood-2002-06-1841. This Article Full Text (PDF) All Versions of this Article: 2002-06-1841v1 101/9/3560    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 Dong, R. Articles by Lombardi, G. Search for Related Content PubMed PubMed Citation Articles by Dong, R. Articles by Lombardi, G. Social Bookmarking                   What's this? Submitted June 21, 2002 Accepted December 17, 2002 Dendritic cells from CML patients have altered actin organization, reduced antigen processing and impaired migration Rong Dong, Kate Cwynarski, Alan Entwistle, Federica Marelli-Berg, Francesco Dazzi, Elizabeth Simpson, John M Goldman, Junia V Melo, Robert I Lechler, Ilaria Bellantuono, Anne Ridley, and Giovanna Lombardi* Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, United Kingdom Department of Haematology, Division of Investigative Sciences, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, United Kingdom Transplantation Biology Group, MRC Clinical Sciences Centre, Imperial College at Hammersmith Hospital, London, United Kingdom The Ludwig Institute for Cancer Research and Department of Biochemistry, University College, London, United Kingdom * Corresponding author; email: g.lombardi{at}ic.ac.uk. Chronic myeloid leukaemia (CML) is characterised by expression of the BCR-ABL fusion gene that encodes a 210-kDa protein, which is a constitutively active tyrosine kinase. At least 70% of the oncoprotein is localised to the cytoskeleton and several of the most prominent tyrosine kinase substrates for p210BCR-ABL are cytoskeletal proteins. Dendritic cells (DCs) are bone marrow derived antigen-presenting cells responsible for the initiation of immune responses. In CML patients up to 98% of myeloid DCs generated from peripheral blood mononuclear cells are BCR-ABL positive. In this study we have compared the morphology and behaviour of myeloid DCs derived from CML patients with control DCs from healthy individuals. We show that the actin cytoskeleton and shape of CML-DCs of myeloid origin adherent to fibronectin differ significantly from those of normal DCs. CML-DCs are also defective in processing and presentation of exogenous antigens such as tetanous toxoid. The antigen-processing defect may be a consequence of the reduced capacity of CML-DCs to capture antigen via macropinocytosis or via mannose receptors when compared to DCs generated from healthy individuals. Furthermore chemokine-induced migration of CML-DCs in vitro was significantly reduced. These observations cannot be explained by a difference in the maturation status of CML and normal DCs since phenotypic analysis by flow cytometry showed a similar surface expression of maturation makers. Taken together these results suggest that the defects in antigen processing and migration we have observed in CML-DCs may be related to underlying cytoskeletal changes induced by the p210BCR-ABL fusion protein. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Mumprecht, C. Claus, C. Schurch, V. Pavelic, M. S. Matter, and A. F. 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