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Blood, 1 March 2004, Vol. 103, No. 5, pp. 1815-1822. Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-03-0802. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0802v1 103/5/1815    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 Tabe, Y. Articles by Andreeff, M. Search for Related Content PubMed PubMed Citation Articles by Tabe, Y. Articles by Andreeff, M. Related Collections Neoplasia Apoptosis Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA PML-RAR is associated with leptin-receptor induction: the role of mesenchymal stem cell–derived adipocytes in APL cell survival Yoko Tabe, Marina Konopleva, Mark F. Munsell, Frank C. Marini, Claudia Zompetta, Teresa McQueen, Twee Tsao, Shourong Zhao, Sherry Pierce, Jun Igari, Elihu H. Estey, and Michael Andreeff From the Section of Molecular Hematology and Therapy, Department of Blood and Marrow Transplantation, Department of Biostatistics, and Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX; and the Department of Clinical Pathology, Juntendo University of Medicine, Tokyo, Japan. Leptin is secreted by bone marrow (BM) adipocytes and stromal cells and was shown to stimulate myeloid proliferation. We here report that primary acute promyelocytic leukemia (APL) cells express high levels of the leptin-receptor (OB-R) long isoform. In cells with regulated promyelocytic leukemia–retinoic acid receptor (PML-RAR) expression, inducing PML-RAR was found to increase OB-R levels. We then investigated the effects of leptin produced by BM adipocytes on APL cells using a coculture system with mesenchymal stem cell (MSC)–derived adipocytes. In PML-RAR–expressing cells, all-trans retinoic acid (ATRA)– and doxorubicin-induced apoptosis were significantly reduced by coculture with adipocyte-differentiated MSCs. This antiapoptotic effect required direct cell-to-cell interactions, was associated with phosphorylation of signal transducer and activator of transcription-3 (STAT3) and mitogen-activated protein kinase (MAPK), and was reduced by blocking OB-R. This report provides a mechanistic basis for the BM adipocyte–leukemia cell interaction and suggests that OB-R receptor blockade may have therapeutic use in APL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Samudio, M. Fiegl, T. McQueen, K. Clise-Dwyer, and M. Andreeff The Warburg Effect in Leukemia-Stroma Cocultures Is Mediated by Mitochondrial Uncoupling Associated with Uncoupling Protein 2 Activation Cancer Res., July 1, 2008; 68(13): 5198 - 5205. [Abstract] [Full Text] [PDF] L. Jin, Y. Tabe, S. Konoplev, Y. Xu, C. E. Leysath, H. Lu, S. Kimura, A. Ohsaka, M.-B. Rios, L. Calvert, et al. CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells Mol. Cancer Ther., January 1, 2008; 7(1): 48 - 58. [Abstract] [Full Text] [PDF] J. Tolar, A. J. Nauta, M. J. Osborn, A. Panoskaltsis Mortari, R. T. McElmurry, S. Bell, L. Xia, N. Zhou, M. Riddle, T. M. Schroeder, et al. Sarcoma Derived from Cultured Mesenchymal Stem Cells Stem Cells, February 1, 2007; 25(2): 371 - 379. [Abstract] [Full Text] [PDF] A. Schaffler, U. Muller-Ladner, J. Scholmerich, and C. Buchler Role of Adipose Tissue as an Inflammatory Organ in Human Diseases Endocr. Rev., August 1, 2006; 27(5): 449 - 467. [Abstract] [Full Text] [PDF] Y. Tabe, L. Jin, G. B. Mills, Y. Tsutsumi-Ishii, M. Andreeff, and M. Konopleva Mesenchymal Stem Cells Promote Survival of Leukemic Cells Via Integrin-Linked Kinase (ILK)-Dependent Akt and STAT3 Activation: Implications for Leukemia Therapy. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 3377 - 3377. [Abstract] V. C. Russo, S. Metaxas, K. Kobayashi, M. Harris, and G. A. Werther Antiapoptotic Effects of Leptin in Human Neuroblastoma Cells Endocrinology, September 1, 2004; 145(9): 4103 - 4112. [Abstract] [Full Text] [PDF]

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