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Prepublished online as a Blood First Edition Paper on March 13, 2003; DOI 10.1182/blood-2002-08-2369. This Article Full Text (PDF) All Versions of this Article: 2002-08-2369v1 102/1/87    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 Zeuner, A. Articles by De Maria, R. Search for Related Content PubMed PubMed Citation Articles by Zeuner, A. Articles by De Maria, R. Social Bookmarking                   What's this? Submitted August 2, 2002 Accepted January 16, 2003 Stem cell factor protects erythroid precursor cells from chemotherapeutic agents via upregulation of Bcl-2 family proteins Ann Zeuner, Francesca Pedini, Michele Signore, Ugo Testa, Elvira Pelosi, Cesare Peschle, and Ruggero De Maria* Laboratory of Hematology-Oncology, Istituto Superiore di Sanita', Rome, Italy Department of Experimental Oncology, Istituto Oncologico del Mediterraneo, Catania, Italy Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA * Corresponding author; email: rdemaria{at}tin.it. Suppression of red blood cell production is a common complication of chemotherapy, causing anemia in a significant number of cancer patients. We have evaluated the sensitivity of human hematopoietic progenitors and erythroid precursor cells to chemotherapeutic drugs and found that basophilic erythroblasts represent the stage of erythroid differentiation more vulnerable to the cytotoxic effects of myelosuppressive agents. Stem cell factor (SCF) supports proliferation and survival of early hematopoietic cells by binding to the c-kit receptor. In unilineage erythropoietic culture of CD34+ progenitors, short term pretreatment of immature erythroid precursors with SCF results in protection from apoptosis induced by chemotherapeutic agents and restores normal proliferation and differentiation after removal of the cytotoxic stimulus. The levels of drug-induced caspase processing are significantly reduced in erythroblasts treated with SCF, indicating that activation of the c-kit receptor generates anti-apoptotic signals acting before amplification of the caspase cascade. Accordingly, we found that SCF upregulates Bcl-2 and Bcl-XL in erythroid precursors and that exogenous expression of these proteins protects erythroblasts from caspase activation and death induced by chemotherapeutic agents. These results suggest a possible mechanism for SCF-mediated protection of erythroid precursor cells from apoptosis and may contribute to devise new strategies for prevention and treatment of chemotherapy-induced anemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zeuner, F. Pedini, F. Francescangeli, M. Signore, G. Girelli, A. Tafuri, and R. De Maria Activity of the BH3 mimetic ABT-737 on polycythemia vera erythroid precursor cells Blood, February 12, 2009; 113(7): 1522 - 1525. [Abstract] [Full Text] [PDF] B. Hu and L. M. Colletti Stem cell factor and c-kit are involved in hepatic recovery after acetaminophen-induced liver injury in mice Am J Physiol Gastrointest Liver Physiol, July 1, 2008; 295(1): G45 - G53. [Abstract] [Full Text] [PDF] M. Gabbianelli, O. Morsilli, A. Massa, L. Pasquini, P. Cianciulli, U. Testa, and C. Peschle Effective erythropoiesis and HbF reactivation induced by kit ligand in -thalassemia Blood, January 1, 2008; 111(1): 421 - 429. [Abstract] [Full Text] [PDF] J. Tu, L. Fan, K. Tao, W. Zhu, J. Li, and G. Lu Stem cell factor affects fate determination of human gonocytes in vitro Reproduction, December 1, 2007; 134(6): 757 - 765. [Abstract] [Full Text] [PDF] A. Zeuner, M. Signore, D. Martinetti, M. Bartucci, C. Peschle, and R. De Maria Chemotherapy-Induced Thrombocytopenia Derives from the Selective Death of Megakaryocyte Progenitors and Can Be Rescued by Stem Cell Factor Cancer Res., May 15, 2007; 67(10): 4767 - 4773. [Abstract] [Full Text] [PDF] A. Bashamboo, A. H. Taylor, K. Samuel, J.-J. Panthier, A. D. Whetton, and L. M. Forrester The survival of differentiating embryonic stem cells is dependent on the SCF-KIT pathway J. Cell Sci., August 1, 2006; 119(15): 3039 - 3046. [Abstract] [Full Text] [PDF] Y. Ohene-Abuakwa, K. A. Orfali, C. Marius, and S. E. Ball Two-phase culture in Diamond Blackfan anemia: localization of erythroid defect Blood, January 15, 2005; 105(2): 838 - 846. [Abstract] [Full Text] [PDF] A. Catalano, S. Rodilossi, M. R. Rippo, P. Caprari, and A. Procopio Induction of Stem Cell Factor/c-Kit/Slug Signal Transduction in Multidrug-resistant Malignant Mesothelioma Cells J. Biol. Chem., November 5, 2004; 279(45): 46706 - 46714. [Abstract] [Full Text] [PDF]

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