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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.
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https://hal.sorbonne-universite.fr/hal-02558548
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Submitted on : Wednesday, April 29, 2020 - 4:49:40 PM
Last modification on : Tuesday, February 2, 2021 - 9:34:02 PM

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Aurore Perrot, Cédric Pionneau, Sophie Nadaud, Frederic Davi, Véronique Leblond, et al.. A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia. Blood, American Society of Hematology, 2011, 118 (4), pp.e1-e15. ⟨10.1182/blood-2011-02-335125⟩. ⟨hal-02558548⟩

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