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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3722-3730.
Prepublished online as a Blood First Edition Paper on January 13, 2005; DOI 10.1182/blood-2004-10-3999.
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NEOPLASIA
Proteomic analysis of mantle-cell lymphoma by protein microarray
Irene M. Ghobrial,
Daniel J. McCormick,
Scott H. Kaufmann,
Alexey A. Leontovich,
David A. Loegering,
Nga T. Dai,
Kelly L. Krajnik,
Mary J. Stenson,
Mona F. Melhem,
Anne J. Novak,
Stephen M. Ansell, and
Thomas E. Witzig
From the Division of Hematology, Department of Internal Medicine; the Proteomic Core, Biochemistry and Molecular Biology; the Department of Oncology; the Genomics Core, Molecular Biology; and Experimental Pathology, Department of Pathology, Mayo Clinic, Rochester, MN; and the Department of Pathology, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, PA.
Mantle-cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphoma (NHL) that behaves aggressively and remains incurable. In order to understand the pathogenesis of MCL and design new therapies, it is important to accurately analyze molecular changes in pathways dysregulated in MCL. We used antibody microarrays to compare patterns of protein expression between CD19+ purified B lymphocytes from normal tonsil and 7 cases of histologically confirmed MCL. Protein overexpression was defined as a higher than 1.3-fold or 2-fold increase in at least 67% of tumor samples compared with normal B-cell control. Of the polypeptides, 77 were overexpressed using the higher than 1.3-fold cutoff, and 13 were overexpressed using the 2-fold cutoff. These included cell cycle regulators (regulator of chromosome condensation 1 [RCC1], murine double minute 2 [MDM2]), a kinase (citron Rho-interacting kinase [CRIK]), chaperone proteins (heat shock 90-kDa protein [Hsp90], Hsp10), and phosphatase regulators (A-kinase anchor protein 1 [AKAP149], protein phosphatase 5 [PP5], and inhibitor 2). The elevated expression of some of these polypeptides was confirmed by immunoblotting and immunohistochemistry, whereas elevated expression of others could not be confirmed, illustrating the importance of confirmatory studies. This study describes a novel technique that identifies proteins dysregulated in MCL.
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