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Blood, 1 April 2007, Vol. 109, No. 7, pp. 3031-3041. Prepublished online as a Blood First Edition Paper on November 16, 2006; DOI 10.1182/blood-2006-07-032714. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-07-032714v1 109/7/3031    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 Aichberger, K. J. Articles by Valent, P. Search for Related Content PubMed PubMed Citation Articles by Aichberger, K. J. Articles by Valent, P. Related Collections Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Identification of MCL1 as a novel target in neoplastic mast cells in systemic mastocytosis: inhibition of mast cell survival by MCL1 antisense oligonucleotides and synergism with PKC412 Karl J. Aichberger1, Matthias Mayerhofer1, Karoline V. Gleixner1, Maria-Theresa Krauth1, Alexander Gruze2, Winfried F. Pickl2, Volker Wacheck3, Edgar Selzer4, Leonhard Müllauer5, Hermine Agis1, Christian Sillaber1, and Peter Valent1 1 Department of Internal Medicine I, Division of Hematology and Hemostaseology, 2 Institute of Immunology, 3 Department of Clinical Pharmacology, 4 Department of Radiation Therapy, 5 Department of Clinical Pathology, Medical University of Vienna, Austria MCL-1 is a Bcl-2 family member that has been described as antiapoptotic in various myeloid neoplasms. Therefore, MCL-1 has been suggested as a potential new therapeutic target. Systemic mastocytosis (SM) is a myeloid neoplasm involving mast cells (MCs) and their progenitors. In the present study, we examined the expression and functional role of MCL-1 in neoplastic MCs and sought to determine whether MCL-1 could serve as a target in SM. As assessed by RT-PCR and immunohistochemical examination, primary neoplastic MCs expressed MCL-1 mRNA and the MCL-1 protein in all SM patients examined. Moreover, MCL-1 was detectable in both subclones of the MC line HMC-1—HMC-1.1 cells, which lack the SM-related KIT mutation D816V, and HMC-1.2 cells, which carry KIT D816V. Exposure of HMC-1.1 cells or HMC-1.2 cells to MCL-1–specific antisense oligonucleotides (ASOs) or MCL-1–specific siRNA resulted in reduced survival and increased apoptosis compared with untreated cells. Moreover, MCL-1 ASOs were found to cooperate with various tyrosine kinase inhibitors in producing growth inhibition in neoplastic MCs, with synergistic effects observed with PKC412, AMN107, and imatinib in HMC-1.1 cells and with PKC412 in HMC-1.2 cells. Together, these data show that MCL-1 is a novel survival factor and an attractive target in neoplastic MCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Targeting the mast cell: beyond KIT Cem Akin Blood 2007 109: 2674-2675. [Full Text] [PDF] This article has been cited by other articles: M. Mayerhofer, K. V. Gleixner, J. Mayerhofer, G. Hoermann, E. Jaeger, K. J. Aichberger, R. G. Ott, K. Greish, H. Nakamura, S. Derdak, et al. Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib Blood, February 15, 2008; 111(4): 2200 - 2210. [Abstract] [Full Text] [PDF] M.T. Krauth, M. Fodinger, L. Rebuzzi, R. Greul, A. Chott, and P. Valent Aggressive systemic mastocytosis with sarcoma-like growth in the skeleton, leukemic progression, and partial loss of mast cell differentiation antigens Haematologica, December 1, 2007; 92(12): e126 - e129. [Full Text] [PDF] E. Voisset, S. Lopez, P. Dubreuil, and P. De Sepulveda The tyrosine kinase FES is an essential effector of KITD816V proliferation signal Blood, October 1, 2007; 110(7): 2593 - 2599. [Abstract] [Full Text] [PDF]

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