Proteomic analysis of Waldenstrom macroglobulinemia

Evdoxia Hatjiharissi, Hai Ngo, Alexey A. Leontovich, Xavier Leleu, Michael Timm, Mona Melhem, Diane George, Ganwei Lu, Joanna Ghobrial, Yazan Alsayed, Steven Zeismer, Miguel Cabanela, Alex Nehme, Xiaoying Jia, Anne Sophie Moreau, Steven P. Treon, Rafael Fonseca, Morie A. Gertz, Kenneth C. Anderson, Thomas E. WitzigIrene M. Ghobrial

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

To better understand the molecular changes that occur in Waldenstrom macroglobulinemia (WM), we employed antibody-based protein microarrays to compare patterns of protein expression between untreated WM and normal bone marrow controls. Protein expression was defined as a >2-fold or 1.3-fold change in at least 67% of the tumor samples. Proteins up-regulated by >2-fold included Ras family proteins, such as Rab-4 and p62DOK, and Rho family proteins, such as CDC42GAP and ROKα. Other proteins up-regulated by >1.3-fold included cyclin-dependent kinases, apoptosis regulators, and histone deacetylases (HDAC). We then compared the samples of patients with symptomatic and asymptomatic WM and showed similar protein expression signatures, indicating that the dysregulation of signaling pathways occurs early in the disease course. Three proteins were different by >2-fold in symptomatic versus asymptomatic, including the heat shock protein HSP90. Elevated protein expression was confirmed by immunohistochemistry and immunoblotting. Functional significance was validated by the induction of apoptosis and inhibition of proliferation using specific HDAC and HSP90 inhibitors. This study, therefore, identifies, for the first time, multiple novel proteins that are dysregulated in WM, which both enhance our understanding of disease pathogenesis and represent targets of novel therapeutics.

Original languageEnglish (US)
Pages (from-to)3777-3784
Number of pages8
JournalCancer research
Volume67
Issue number8
DOIs
StatePublished - Apr 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hatjiharissi, E., Ngo, H., Leontovich, A. A., Leleu, X., Timm, M., Melhem, M., George, D., Lu, G., Ghobrial, J., Alsayed, Y., Zeismer, S., Cabanela, M., Nehme, A., Jia, X., Moreau, A. S., Treon, S. P., Fonseca, R., Gertz, M. A., Anderson, K. C., ... Ghobrial, I. M. (2007). Proteomic analysis of Waldenstrom macroglobulinemia. Cancer research, 67(8), 3777-3784. https://doi.org/10.1158/0008-5472.CAN-06-3089