SEARCH:   Advanced

Blood, 12 November 2009, Vol. 114, No. 20, pp. 4441-4450. Prepublished online as a Blood First Edition Paper on September 17, 2009; DOI 10.1182/blood-2009-07-233718. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-07-233718v1 114/20/4441    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 CrossRef Google Scholar Articles by Kurtova, A. V. Articles by Burger, J. A. PubMed PubMed Citation Articles by Kurtova, A. V. Articles by Burger, J. A. Related Collections Lymphoid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Diverse marrow stromal cells protect CLL cells from spontaneous and drug-induced apoptosis: development of a reliable and reproducible system to assess stromal cell adhesion-mediated drug resistance Antonina V. Kurtova1, Kumudha Balakrishnan2, Rong Chen2, Wei Ding3, Susanne Schnabl4, Maite P. Quiroga1, Mariela Sivina1, William G. Wierda1, Zeev Estrov1, Michael J. Keating1, Medhat Shehata4, Ulrich Jäger4, Varsha Gandhi2, Neil E. Kay3, William Plunkett2, and Jan A. Burger1 Departments of 1 Leukemia, and 2 Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston; 3 Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN; and 4 Internal Medicine I, and K. Landsteiner Institute for Cytokine and Tumor Microenvironment, Medical University of Vienna, Vienna, Austria Marrow stromal cells (MSCs) provide important survival and drug resistance signals to chronic lymphocytic leukemia (CLL) cells, but current models to analyze CLL–MSC interactions are heterogeneous. Therefore, we tested different human and murine MSC lines and primary human MSCs for their ability to protect CLL cells from spontaneous and drug-induced apoptosis. Our results show that both human and murine MSCs are equally effective in protecting CLL cells from fludarabine-induced apoptosis. This protective effect was sustained over a wide range of CLL–MSC ratios (5:1 to 100:1), and the levels of protection were reproducible in 4 different laboratories. Human and murine MSCs also protected CLL cells from dexamethasone- and cyclophosphamide-induced apoptosis. This protection required cell–cell contact and was virtually absent when CLL cells were separated from the MSCs by micropore filters. Furthermore, MSCs maintained Mcl-1 and protected CLL cells from spontaneous and fludarabine-induced Mcl-1 and PARP cleavage. Collectively, these studies define common denominators for CLL cocultures with MSCs. They also provide a reliable, validated tool for future investigations into the mechanism of MSC–CLL cross talk and for drug testing in a more relevant fashion than the commonly used suspension cultures. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020