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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-06-1743. This Article Full Text (PDF) Supplemental Data Sets All Versions of this Article: 2002-06-1743v1 101/11/4598    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 Vallat, L. Articles by Delic, J. Search for Related Content PubMed PubMed Citation Articles by Vallat, L. Articles by Delic, J. Social Bookmarking                   What's this? Submitted June 27, 2002 Accepted January 28, 2003 The resistance of B-CLL cells to DNA damage-induced apoptosis defined by DNA microarrays Laurent Vallat, Henri Magdelenat, Helene Merle-Beral, Peggy Masdehors, Gabrielle Potocki de Montalk, Frederic Davi, Mogens Kruhoffer, Laure Sabatier, Torben F Orntoft, and Jozo Delic* Laboratoire de Radiobiologie et Oncologie, CEA, DSV/DRR, Fontenay aux Roses, France; Hematology/Biology, Hospital Pitie-Salpetriere, Paris, France Laboratoire de Physiopathology, Institute Curie, Paris, France Hematology/Biology, Hospital Pitie-Salpetriere, Paris, France Laboratoire de Radiobiologie et Oncologie, CEA, DSV/DRR, Fontenay aux Roses, France Clinical Biochemistry, Universitethospital, Aarhus, Denmark * Corresponding author; email: delic{at}dsvidf.cea.fr. B-cell chronic lymphoid leukemia (B-CLL) is a highly heterogeneous human malignancy, presumably reflecting specific molecular alterations in gene expression and protein activity which are thought to underlie the variable disease outcome. The majority of B-CLL cell samples undergo apoptotic death in response to DNA damage. However, a clinically distinct aggressive subset of B-CLL is completely resistant to in vitro activation of the apoptotic death pathway. We therefore compared gene expression patterns in resistant and sensitive B-CLL cell subsets. DNA microarray analysis was performed for four sensitive and three resistant B-CLL cell samples, before and after apoptotic stimuli, and the specific expression patterns of the selected genes were confirmed by quantitative real-time PCR. We selected 16 genes whose expression varied at least two-fold specifically in resistant cells. Furthermore, we confirmed the expression of these selected genes by real-time PCR on 15 additional B-CLL cell samples not included in the microarray analysis. In this manner, 13 genes were found to be specific for all resistant B-CLL cell samples tested: nuclear orphan receptor TR3, MHC class II glycoprotein HLA-DQA1, mtmr6, c-myc, c-rel, c-IAP1, mat2A and fmod were upregulated while MIP1/GOS19-1 homolog, stat1, blk, hsp27 and ech1 were downregulated. In some cases, the expression profile was dependent on the status of p53. Some of these genes encode general apoptotic factors but also exhibit lymphoid cell specificities which could potentially be linked to the development of lymphoid malignancies (MIP1, blk, TR3, mtmr6). Taken together, our data define new molecular markers specific to resistant B-CLLs which might be of clinical relevance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Zou, S.-C. 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