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Blood, 8 October 2009, Vol. 114, No. 15, pp. 3299-3308. Prepublished online as a Blood First Edition Paper on July 22, 2009; DOI 10.1182/blood-2008-07-170282. This Article Full Text Full Text (PDF) Supplemental Methods, Tables, and Figures All Versions of this Article: blood-2008-07-170282v1 114/15/3299    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 CrossRef Google Scholar Articles by Oehler, V. G. Articles by Radich, J. P. PubMed PubMed Citation Articles by Oehler, V. G. Articles by Radich, J. P. Related Collections Myeloid Neoplasia Phagocytes, Granulocytes, and Myelopoiesis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells Vivian G. Oehler1, Katherine A. Guthrie1, Carrie L. Cummings1, Kathleen Sabo2, Brent L. Wood3, Ted Gooley1, Taimei Yang1, Mirjam T. Epping4, Yaping Shou5, Era Pogosova-Agadjanyan1, Paula Ladne1, Derek L. Stirewalt1, Janis L. Abkowitz2, and Jerald P. Radich1 1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2 Division of Hematology, University of Washington, Seattle; 3 Department of Laboratory Medicine, Hematopathology, University of Washington, Seattle; 4 Division of Molecular Carcinogenesis, Netherlands Cancer Institute, Amsterdam, The Netherlands; and 5 Novartis Institutes for BioMedical Research, Novartis Pharmaceuticals Corporation, Cambridge, MA The preferentially expressed antigen in melanoma (PRAME) is expressed in several hematologic malignancies, but either is not expressed or is expressed at only low levels in normal hematopoietic cells, making it a target for cancer therapy. PRAME is a tumor-associated antigen and has been described as a corepressor of retinoic acid signaling in solid tumor cells, but its function in hematopoietic cells is unknown. PRAME mRNA expression increased with chronic myeloid leukemia (CML) disease progression and its detection in late chronic-phase CML patients before tyrosine kinase inhibitor therapy was associated with poorer therapeutic responses and ABL tyrosine kinase domain point mutations. In leukemia cell lines, PRAME protein expression inhibited granulocytic differentiation only in cell lines that differentiate along this lineage after all-trans retinoic acid (ATRA) exposure. Forced PRAME expression in normal hematopoietic progenitors, however, inhibited myeloid differentiation both in the presence and absence of ATRA, and this phenotype was reversed when PRAME was silenced in primary CML progenitors. These observations suggest that PRAME inhibits myeloid differentiation in certain myeloid leukemias, and that its function in these cells is lineage and phenotype dependent. Lastly, these observations suggest that PRAME is a target for both prognostic and therapeutic applications. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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