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Blood, 24 December 2009, Vol. 114, No. 27, pp. 5512-5521. Prepublished online as a Blood First Edition Paper on October 14, 2009; DOI 10.1182/blood-2009-02-204834. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2009-02-204834v1 114/27/5512    most recent e-Letter: Submit a Response Alert me when this article is cited Alert me when e-Letters are posted 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 Luesink, M. Articles by Jansen, J. H. Search for Related Content PubMed PubMed Citation Articles by Luesink, M. Articles by Jansen, J. H. Related Collections Myeloid Neoplasia Related Article in Blood Online Social Bookmarking                         What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome Maaike Luesink1,*, Jeroen L. A. Pennings1,2,*, Willemijn M. Wissink1, Peter C. M. Linssen1, Petra Muus1, Rolph Pfundt3, Theo J. M. de Witte1, Bert A. van der Reijden1, and Joop H. Jansen1 1 Central Hematology Laboratory and Department of Hematology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen; 2 Laboratory for Health Protection Research, National Institute for Public Health and the Environment, Bilthoven; and 3 Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) and/or arsenic trioxide can induce a differentiation syndrome (DS) with massive pulmonary infiltration of differentiating leukemic cells. Because chemokines are implicated in migration and extravasation of leukemic cells, chemokines might play a role in DS. ATRA stimulation of the APL cell line NB4 induced expression of multiple CC-chemokines (CCLs) and their receptors (> 19-fold), resulting in increased chemokine levels and chemotaxis. Induction of CCL2 and CCL24 was directly mediated by ligand-activated retinoic acid receptors. In primary leukemia cells derived from APL patients at diagnosis, ATRA induced chemokine production as well. Furthermore, in plasma of an APL patient with DS, we observed chemokine induction, suggesting that chemokines might be important in DS. Dexamethasone, which efficiently reduces pulmonary chemokine production, did not inhibit chemokine induction in APL cells. Finally, chemokine production was also induced by arsenic trioxide as single agent or in combination with ATRA. We propose that differentiation therapy may induce chemokine production in the lung and in APL cells, which both trigger migration of leukemic cells. Because dexamethasone does not efficiently reduce leukemic chemokine production, pulmonary infiltration of leukemic cells may induce an uncontrollable hyperinflammatory reaction in the lung. CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this? Related Article in Blood Online: CCL2/CCR2: push/pull for migration Giuseppe Avvisati Blood 2009 114: 5411-5412. [Full Text] [PDF] This article has been cited by other articles: G. Avvisati CCL2/CCR2: push/pull for migration Blood, December 24, 2009; 114(27): 5411 - 5412. [Full Text] [PDF]

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