Proteomic analysis of mantle-cell lymphoma by protein microarray

Irene M. Ghobrial, Daniel J Mc Cormick, Scott H Kaufmann, Alexey A. Leontovich, David A. Loegering, Nga T. Dai, Kelly L. Krajnik, Mary J. Stenson, Mona F. Meinem, Anne J Novak, Stephen Maxted Ansell, Thomas Elmer Witzig

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3722-3730
Number of pages9
JournalBlood
Volume105
Issue number9
DOIs
StatePublished - May 1 2005

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Mantle-Cell Lymphoma
Protein Array Analysis
Microarrays
Proteomics
Cells
A Kinase Anchor Proteins
Proteins
HSP90 Heat-Shock Proteins
Chaperonin 10
B-Lymphocytes
Peptides
Lymphocytes
Chromosomes
Phosphoric Monoester Hydrolases
Chromosomes, Human, Pair 1
Palatine Tonsil
Tumors
B-Cell Lymphoma
Condensation
Immunoblotting

ASJC Scopus subject areas

  • Hematology

Cite this

Proteomic analysis of mantle-cell lymphoma by protein microarray. / Ghobrial, Irene M.; Mc Cormick, Daniel J; Kaufmann, Scott H; Leontovich, Alexey A.; Loegering, David A.; Dai, Nga T.; Krajnik, Kelly L.; Stenson, Mary J.; Meinem, Mona F.; Novak, Anne J; Ansell, Stephen Maxted; Witzig, Thomas Elmer.

In: Blood, Vol. 105, No. 9, 01.05.2005, p. 3722-3730.

Research output: Contribution to journalArticle

Ghobrial, IM, Mc Cormick, DJ, Kaufmann, SH, Leontovich, AA, Loegering, DA, Dai, NT, Krajnik, KL, Stenson, MJ, Meinem, MF, Novak, AJ, Ansell, SM & Witzig, TE 2005, 'Proteomic analysis of mantle-cell lymphoma by protein microarray', Blood, vol. 105, no. 9, pp. 3722-3730. https://doi.org/10.1182/blood-2004-10-3999
Ghobrial, Irene M. ; Mc Cormick, Daniel J ; Kaufmann, Scott H ; Leontovich, Alexey A. ; Loegering, David A. ; Dai, Nga T. ; Krajnik, Kelly L. ; Stenson, Mary J. ; Meinem, Mona F. ; Novak, Anne J ; Ansell, Stephen Maxted ; Witzig, Thomas Elmer. / Proteomic analysis of mantle-cell lymphoma by protein microarray. In: Blood. 2005 ; Vol. 105, No. 9. pp. 3722-3730.
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