A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia.

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course with 2 extreme subsets: indolent, ZAP70(-) and mutated immunoglobulin heavy chain gene (M-CLL); and aggressive, ZAP70(+) and unmutated immunoglobulin heavy chain (UM-CLL). Given the long-term suspicion of antigenic stimulation as a primum movens in the disease, the role of the B-cell receptor has been extensively studied in various experimental settings; albeit scarcely in a comparative dynamic proteomic approach. Here we use a quantitative 2-dimensional fluorescence difference gel electrophoresis technology to compare 48 proteomic profiles of the 2 CLL subsets before and after anti-IgM ligation. Differentially expressed proteins were subsequently identified by mass spectrometry. We show that unstimulated M- and UM-CLL cells display distinct proteomic profiles. Furthermore, anti-IgM stimulation induces a specific proteomic response, more pronounced in the more aggressive CLL. Statistical analyses demonstrate several significant protein variations according to stimulation conditions. Finally, we identify an intermediate form of M-CLL cells, with an indolent profile (ZAP70(-)) but sharing aggressive proteomic profiles alike UM-CLL cells. Collectively, this first quantitative and dynamic proteome analysis of CLL further dissects the complex molecular pathway after B-cell receptor stimulation and depicts distinct proteomic profiles, which could lead to novel molecular stratification of the disease.

• Authors: Aurore Perrot, Cédric Pionneau, Sophie Nadaud, Frédéric Davi, Véronique Leblond, Frédéric Jacob, Hélène Merle-Béral, Raoul Herbrecht, Marie-Christine Béné, John G Gribben, Seiamak Bahram, Laurent Vallat
• Journal: Blood (Blood) Vol. 118 Issue 4 Pg. e1-15 (Jul 28 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21602524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)

Chemical References

• Boronic Acids
• Protease Inhibitors
• Pyrazines
• Bortezomib

Topics

• Amyloidosis (drug therapy)
• Boronic Acids (administration & dosage)
• Bortezomib
• Female
• Humans
• Immunoglobulin Light-chain Amyloidosis
• Male
• Protease Inhibitors (administration & dosage)
• Pyrazines (administration & dosage)