A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia.
Fiche publication
Date publication
juillet 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Pr HERBRECHT Raoul, Dr VALLAT Laurent
Tous les auteurs :
Perrot A, Pionneau C, Nadaud S, Davi F, Leblond V, Jacob F, Merle-Beral H, Herbrecht R, Bene MC, Gribben JG, Bahram S, Vallat L
Lien Pubmed
Résumé
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.
Référence
Blood. 2011 Jul 28;118(4):e1-15