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Blood, 15 July 2007, Vol. 110, No. 2, pp. 661-669. Prepublished online as a Blood First Edition Paper on April 9, 2007; DOI 10.1182/blood-2006-10-054411. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-054411v1 110/2/661    most recent Alert me when this article is cited Alert me if a correction is posted 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 Kondo, R. Articles by Valent, P. Search for Related Content PubMed PubMed Citation Articles by Kondo, R. Articles by Valent, P. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 25, 2006 Accepted March 30, 2007 Identification of heat shock protein 32 (Hsp32) as a novel survival factor and therapeutic target in neoplastic mast cells Rudin Kondo, Karoline V Gleixner, Matthias Mayerhofer, Anja Vales, Alexander Gruze, Puchit Samorapoompichit, Khaled Greish, Maria-Theresa Krauth, Karl J. Aichberger, Winfried F. Pickl, Harald Esterbauer, Christian Sillaber, Hiroshi Maeda, and Peter Valent* Dept of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria Clinical Inst. of Medical & Chemical Laboratory Diagnostics, Medical University of Vienna, Vienna, Austria Institute of Immunology, Medical University of Vienna, Vienna, Austria Center of Anatomy & Cell Biology, Medical University of Vienna, Vienna, Austria Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan * Corresponding author; email: peter.valent{at}meduniwien.ac.at. Systemic mastocytosis (SM) is a myeloid neoplasm characterized by increased survival and accumulation of neoplastic mast cells (MC). In most patients, the D816V-mutated variant of KIT is detectable. We report that heat shock protein 32 (Hsp32), also known as heme oxygenase-1 (HO-1), is a novel KIT-inducible survival factor in neoplastic MC. As assessed by RT-PCR, immunocytochemistry, and Western blotting, the KIT D816V-positive MC line HMC-1.2 as well as highly enriched primary neoplastic MC were found to express Hsp32 mRNA and the Hsp32 protein. Moreover, KIT D816V and SCF-activated wild-type-KIT were found to induce Hsp32-promoter-activity, expression of Hsp32-mRNA, and expression of the Hsp32 protein in Ba/F3 cells. Correspondingly, the KIT-D816V-targeting drug PKC412 decreased the expression of Hsp32 as well as proliferation/survival in neoplastic MC. The inhibitory effects of PKC412 on survival of HMC-1.2 cells were counteracted by the HO-1 inductor hemin or lentiviral-transduced HO-1. Moreover, two Hsp32-targeting drugs, pegylated zinc-protoporphyrin (PEG-ZnPP) and styrene maleic acid-micelle-encapsulated ZnPP (SMA-ZnPP), were found to inhibit proliferation and to induce apoptosis in neoplastic MC. Furthermore, both drugs were found to cooperate with PKC412 in producing growth-inhibition. Together, these data show that Hsp32 is an important survival factor and interesting new therapeutic target in neoplastic MC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hsp32: MASTer of KIT? Michel A. Arock Blood 2007 110: 471. [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]

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