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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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Submitted October 18, 2004
Accepted December 31, 2004

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*

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
Proteomic Core, Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA; Department of Oncology, Mayo Clinic, Rochester, MN, USA
Experimental Pathology, Department of Pathology, Mayo Clinic, Rochester, MN, USA
Department of Oncology, Mayo Clinic, Rochester, MN, USA
Genomics Core, Molecular Biology, Mayo Clinic, Rochester, MN, USA
Department of Pathology, VA Pittsburgh Healthcare System, University of Pittsburgh, Pittsburgh, PA, USA

* Corresponding author; email: Witzig.Thomas{at}mayo.edu.

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 employed 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 greater than 1.3-fold or 2-fold increase in at least 67% of tumor samples compared to normal B-cell control. Seventy-seven polypeptides were overexpressed using the >1.3-fold cutoff and thirteen polypeptides were overexpressed using the 2-fold cutoff. These included cell cycle regulators (RCC1, MDM2), a kinase (CRIK), chaperone proteins (Hsp90, Hsp10), and phosphatase regulators (AKAP149, 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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