title: 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: Laboratoire d'Immunogénétique Moléculaire Humaine, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
authors: Aurore
authors: A
authors: Perrot
authors: Cédric
authors: C
authors: Pionneau
authors: Sophie
authors: S
authors: Nadaud
authors: Frédéric
authors: F
authors: Davi
authors: Véronique
authors: V
authors: Leblond
authors: Frédéric
authors: F
authors: Jacob
authors: Hélène
authors: H
authors: Merle-Béral
authors: Raoul
authors: R
authors: Herbrecht
authors: Marie-Christine
authors: MC
authors: Béné
authors: John G
authors: JG
authors: Gribben
authors: Seiamak
authors: S
authors: Bahram
authors: Laurent
authors: L
authors: Vallat
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