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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4614-4626. Prepublished online as a Blood First Edition Paper on February 18, 2009February 24, 2009; DOI 10.1182/blood-2008-07-170464. This Article Full Text (PDF) All Versions of this Article: blood-2008-07-170464v1 blood-2008-07-170464v2 113/19/4614    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sprynski, A. C. Articles by Klein, B. Search for Related Content PubMed PubMed Citation Articles by Sprynski, A. C. Articles by Klein, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 22, 2008 Accepted February 14, 2009 The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor Anne Catherine Sprynski, Dirk Hose, Laurent Caillot, Thierry Reme, John D. Shaughnessy Jr., Bart Barlogie, Anja Seckinger, Jerome Moreaux, Michael Hundemer, Michel Jourdan, Tobias Meissner, Anna Jauch, Karene Mahtouk, Alboukadel Kassambara, Uta Bertsch, Jean Francois Rossi, Hartmut Goldschmidt, and Bernard Klein* INSERM, U847, Montpellier, France Medizinische Klinik V, Universitatsklinikum Heidelberg, Heidelberg, Germany ABCell-Bio, Unit for Cellular Therapy, CHU St Eloi, Montpellier, France CHU Montpellier, Institute of Research in Biotherapy, Montpellier, France Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, United States Nationales Centrum fur Tumorerkrankungen, Heidelberg, Germany Institut fur Humangenetik, Universitatsklinikum Heidelberg, Heidelberg, Germany Universite MONTPELLIER1, UFR Medecine, Montpellier, France * Corresponding author; email: bernard.klein{at}inserm.fr. A plethora of myeloma growth factors (MGF) has been identified, but their relative importance and cooperation has not been determined. We investigated 5 well-documented MGF (IL-6, IGF-1, HGF, HB-EGF, APRIL) in serum-free cultures of human myeloma cell lines (HMCLs). In all of 3 CD45- HMCLs, an autocrine IGF-1 loop promoted autonomous survival. To the contrary, all 5 CD45+ HMCLs could not survive and required addition of either IL-6 (5/5), IGF-1 (4/5), HGF (1/5), HB-EGF (1/5) or APRIL (1/5). IGF-1 was the major MGF since its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF or HB-EGF activity was inhibited by both IGF-1R- and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGF and their receptors, only expressions of IGF-1R and IL-6R in myeloma cells (MMC) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression in MMC, without t(4;14) can also have a poor prognosis. Thus, IGF-1 targeted therapy - eventually in combination with anti-IL-6 therapy - could be promising in a subset of patients with MMC expressing IGF-1R. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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