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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.
 Previous Article | Next Article 
Submitted June 9, 2008
Accepted August 25, 2008
Chronic lymphocytic leukemia antibodies with a common stereotypic rearrangement recognize non-muscle myosin heavy chain IIA
Charles C. Chu*, Rosa Catera, Katerina Hatzi, Xiao-Jie Yan, Lu Zhang, Xiao Bo Wang, Henry M. Fales, Steven L. Allen, Jonathan E. Kolitz, Kanti R. Rai, and Nicholas Chiorazzi
The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY, United States
Laboratory of Applied Mass Spectrometry, NHLBI, NIH, Bethesda, MD, United States
Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center North Shore-LIJ Health System, Manhasset, NY, United States
Department of Medicine, NYU School of Medicine, New York, NY, United States
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, United States
* Corresponding author; email: cchu{at}nshs.edu.
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 ~225 kDa that was identified by mass spectrometry as non-muscle 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.
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