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A unique proteomic profile on surface IgM ligation in unmutated chronic lymphocytic leukemia.
- Source :
-
Blood [Blood] 2011 Jul 28; Vol. 118 (4), pp. e1-15. Date of Electronic Publication: 2011 May 20. - Publication Year :
- 2011
-
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.
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 118
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 21602524
- Full Text :
- https://doi.org/10.1182/blood-2011-02-335125