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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5122-5129. Prepublished online as a Blood First Edition Paper on September 23, 2008; DOI 10.1182/blood-2008-06-162024. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-162024v1 112/13/5122    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 Chu, C. C. Articles by Chiorazzi, N. Search for Related Content PubMed PubMed Citation Articles by Chu, C. C. Articles by Chiorazzi, N. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize nonmuscle myosin heavy chain IIA Charles C. Chu1,2,3, Rosa Catera1, Katerina Hatzi1, Xiao-Jie Yan1, Lu Zhang1, Xiao Bo Wang1, Henry M. Fales4, Steven L. Allen1,2,5, Jonathan E. Kolitz1,2,3, Kanti R. Rai1,2,5, and Nicholas Chiorazzi1,2,5,6 1 The Feinstein Institute for Medical Research, North Shore–Long Island Jewish (LIJ) Health System, Manhasset, NY; 2 Department of Medicine, North Shore University Hospital and LIJ Medical Center, North Shore–LIJ Health System, Manhasset and New Hyde Park, NY; 3 Department of Medicine, New York University School of Medicine, NY; 4 Laboratory of Applied Mass Spectrometry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD; and Departments of 5 Medicine and 6 Cell Biology, Albert Einstein College of Medicine, Bronx, NY Leukemic B lymphocytes of a large group of unrelated chronic lymphocytic leukemia (CLL) patients express an unmutated heavy chain immunoglobulin variable (V) region encoded by IGHV1-69, IGHD3-16, and IGHJ3 with nearly identical heavy and light chain complementarity-determining region 3 sequences. The likelihood that these patients developed CLL clones with identical antibody V regions randomly is highly improbable and suggests selection by a common antigen. Monoclonal antibodies (mAbs) from this stereotypic subset strongly bind cytoplasmic structures in HEp-2 cells. Therefore, HEp-2 cell extracts were immunoprecipitated with recombinant stereotypic subset-specific CLL mAbs, revealing a major protein band at approximately 225 kDa that was identified by mass spectrometry as nonmuscle myosin heavy chain IIA (MYHIIA). Reactivity of the stereotypic mAbs with MYHIIA was confirmed by Western blot and immunofluorescence colocalization with anti-MYHIIA antibody. Treatments that alter MYHIIA amounts and cytoplasmic localization resulted in a corresponding change in binding to these mAbs. The appearance of MYHIIA on the surface of cells undergoing stress or apoptosis suggests that CLL mAb may generally bind molecules exposed as a consequence of these events. Binding of CLL mAb to MYHIIA could promote the development, survival, and expansion of these leukemic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L.-A. Sutton, E. Kostareli, A. Hadzidimitriou, N. Darzentas, A. Tsaftaris, A. Anagnostopoulos, R. Rosenquist, and K. Stamatopoulos Extensive intraclonal diversification in a subgroup of chronic lymphocytic leukemia patients with stereotyped IGHV4-34 receptors: implications for ongoing interactions with antigen Blood, November 12, 2009; 114(20): 4460 - 4468. [Abstract] [Full Text] [PDF] K. Stamatopoulos CLL: promiscuity leads to risks Blood, October 22, 2009; 114(17): 3508 - 3509. [Full Text] [PDF] T. Seiler, M. Woelfle, S. Yancopoulos, R. Catera, W. Li, K. Hatzi, C. Moreno, M. Torres, S. Paul, H. Dohner, et al. Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells Blood, October 22, 2009; 114(17): 3615 - 3624. [Abstract] [Full Text] [PDF] J. A. Burger, P. Ghia, A. Rosenwald, and F. Caligaris-Cappio The microenvironment in mature B-cell malignancies: a target for new treatment strategies Blood, October 15, 2009; 114(16): 3367 - 3375. [Abstract] [Full Text] [PDF] M. P. Quiroga, K. Balakrishnan, A. V. Kurtova, M. Sivina, M. J. Keating, W. G. Wierda, V. Gandhi, and J. A. Burger B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406 Blood, July 30, 2009; 114(5): 1029 - 1037. [Abstract] [Full Text] [PDF] T. J. Kipps Chronic Lymphocytic Leukemia: Advances in Assessing Prognosis and Therapy ASCO Educational Book, January 1, 2009; 2009(1): 385 - 393. [Abstract] [Full Text] [PDF]

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