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Blood, 1 July 2008, Vol. 112, No. 1, pp. 188-195. Prepublished online as a Blood First Edition Paper on February 21, 2008; DOI 10.1182/blood-2007-09-111344. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-09-111344v1 112/1/188    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 Muzio, M. Articles by Ghia, P. PubMed PubMed Citation Articles by Muzio, M. Articles by Ghia, P. Related Collections Neoplasia Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy Marta Muzio1, Benedetta Apollonio1, Cristina Scielzo1, Michela Frenquelli1, Irene Vandoni1, Vassiliki Boussiotis2, Federico Caligaris-Cappio1, and Paolo Ghia1 1 Department of Oncology, Unit and Laboratory of Lymphoid Malignancies, Università Vita-Salute San Raffaele and Istituto Scientifico San Raffaele, Milan, Italy; and 2 Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston Stimulation through the B-cell antigen receptor (BCR) is believed to be involved in the natural history of chronic lymphocytic leukemia (CLL). Some cases respond to the in vitro cross-linking of surface immunoglobulin (sIg) with effective activation. In contrast, the remaining cases do not respond to such stimulation, thereby resembling B cells anergized after antigen encounter in vivo. However the biochemical differences between the 2 groups are ill defined, and in humans the term B-cell anergy lacks a molecular definition. We examined the expression and activation of key molecules involved in signaling pathways originating from the BCR, and we report that a proportion of CLL patients (a) expresses constitutively phosphorylated extracellular signal-regulated kinase (ERK)1/2 in the absence of AKT activation; (b) displays constitutive phosphorylation of MEK1/2 and increased nuclear factor of activated T cells (NF-AT) transactivation; and (c) is characterized by cellular unresponsiveness to sIg ligation. This molecular profile recapitulates the signaling pattern of anergic murine B cells. Our data indicate that constitutive activation of mitogen activated protein (MAP) kinase signaling pathway along with NF-AT transactivation in the absence of AKT activation may also represent the molecular signature of anergic human B lymphocytes. CLL cases with this signature may be taken as a human model of anergic B cells aberrantly expanded. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Signals that maintain leukemic cell viability Janet Plate Blood 2008 112: 1-2. [Full Text] [PDF]

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