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Blood, 15 February 2007, Vol. 109, No. 4, pp. 1660-1668. Prepublished online as a Blood First Edition Paper on October 12, 2006; DOI 10.1182/blood-2006-05-021683. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021683v1 109/4/1660    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Smit, L. A. Articles by Eldering, E. Search for Related Content PubMed PubMed Citation Articles by Smit, L. A. Articles by Eldering, E. Related Collections Neoplasia Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Differential Noxa/Mcl-1 balance in peripheral versus lymph node chronic lymphocytic leukemia cells correlates with survival capacity Laura A. Smit1, Delfine Y.H. Hallaert2,3, René Spijker2,3, Bart de Goeij3, Annelieke Jaspers2,3, Arnon P. Kater2, Marinus H.J. van Oers2, Carel J.M. van Noesel1, and Eric Eldering2,3 1 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands; 2 Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands; 3 Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands The gradual accumulation of chronic lymphocytic leukemia (B-CLL) cells is presumed to derive from proliferation centers in lymph nodes and bone marrow. To what extent these cells possess the purported antiapoptotic phenotype of peripheral B-CLL cells is unknown. Recently, we have described that, in B-CLL samples from peripheral blood, aberrant apoptosis gene expression was not limited to protective changes but also included increased levels of proapoptotic BH3-only member Noxa. Here, we compare apoptosis gene profiles from peripheral blood B-CLL (n = 15) with lymph node B-CLL (> 90% CD5+/CD19+/CD23+ lymphocytes with Ki67+ centers; n = 9). Apart from expected differences in Survivin and Bcl-xL, a prominent distinction with peripheral B-CLL cells was the decreased averaged level of Noxa in lymph nodes. Mcl-1 protein expression showed a reverse trend. Noxa expression could be reduced also in vitro by CD40 stimulation of peripheral blood B-CLL. Direct manipulation of Noxa protein levels was achieved by proteasome inhibition in B-CLL and via RNAi in model cell lines. In each instance, cell viability was directly linked with Noxa levels. These data indicate that suppression of Noxa in the lymph node environment contributes to the persistence of B-CLL at these sites and suggest that therapeutic targeting of Noxa might be beneficial. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Secchiero, E. Melloni, M. Tiribelli, A. Gonelli, and G. Zauli Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells J. Leukoc. Biol., February 1, 2008; 83(2): 434 - 437. [Abstract] [Full Text] [PDF] P. G. Longo, L. Laurenti, S. Gobessi, S. Sica, G. Leone, and D. G. Efremov The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells Blood, January 15, 2008; 111(2): 846 - 855. [Abstract] [Full Text] [PDF] S. Willimott, M. Baou, S. Huf, S. Deaglio, and S. D. Wagner Regulation of CD38 in proliferating chronic lymphocytic leukemia cells stimulated with CD154 and interleukin-4 Haematologica, October 1, 2007; 92(10): 1359 - 1366. [Abstract] [Full Text] [PDF] P. Gomez-Bougie, S. Wuilleme-Toumi, E. Menoret, V. Trichet, N. Robillard, M. Philippe, R. Bataille, and M. Amiot Noxa Up-regulation and Mcl-1 Cleavage Are Associated to Apoptosis Induction by Bortezomib in Multiple Myeloma Cancer Res., June 1, 2007; 67(11): 5418 - 5424. [Abstract] [Full Text] [PDF]

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