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This Article Full Text Full Text (PDF) 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 Müller, C. Articles by Koeffler, H. P. Search for Related Content PubMed PubMed Citation Articles by Müller, C. Articles by Koeffler, H. P. Related Collections Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2000, Vol. 96, No. 12, pp. 3894-3899 NEOPLASIA The aberrant fusion proteins PML-RAR and PLZF-RAR contribute to the overexpression of cyclin A1 in acute promyelocytic leukemia Carsten Müller, Rong Yang, Dorothy J. Park, Hubert Serve, Wolfgang E. Berdel, and H. Phillip Koeffler From the Division of Hematology/Oncology, Cedars-Sinai Research Institute/UCLA School of Medicine, Los Angeles, CA, and the Department of Medicine, Hematology/Oncology, University of Münster, Münster, Germany. Cyclin A1 is a newly discovered cyclin that is overexpressed in certain myeloid leukemias. Previously, the authors found that the frequency of cyclin A1 overexpression is especially high in acute promyelocytic leukemia (APL). In this study, the authors investigated the mechanism of cyclin A1 overexpression in APL cells and showed that the APL-associated aberrant fusion proteins (PML-retinoic acid receptor alpha [PML-RAR] or PLZF-RAR) caused the increased levels of cyclin A1 in these cells. The ectopic expression of either PML-RAR or PLZF-RAR in U937 cells, a non-APL myeloid cell line, led to a dramatic increase of cyclin A1 messenger RNA and protein. This elevation of cyclin A1 was reversed by treatment with all-trans retinoic acid (ATRA) in cells expressing PML-RAR but not PLZF-RAR. ATRA also greatly reduced the high levels of cyclin A1 in the APL cell lines NB4 and UF-1. No effect of ATRA on cyclin A1 levels was found in the ATRA-resistant NB4-R2 cells. Further studies using ligands selective for various retinoic acid receptors suggested that cyclin A1 expression is negatively regulated by activated RAR. Reporter assays showed that PML-RAR led to activation of the cyclin A1 promoter. Addition of ATRA inhibited PML-RAR-induced cyclin A1 promoter activity. Taken together, our data suggest that PML-RAR and PLZF-RAR cause the high-level expression of cyclin A1 seen in acute promyelocytic leukemia. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Restle, M. Farber, C. Baumann, M. Bohringer, K. H. 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