title: Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders.
abstract: Waldenström's macroglobulinemia (WM) is a clonal B-cell lymphoproliferative disorder (LPD) of post-germinal center nature. Despite the fact that the precise molecular pathway(s) leading to WM remain(s) to be elucidated, a hallmark of the disease is the absence of the immunoglobulin heavy chain class switch recombination. Using two-dimensional gel electrophoresis, we compared proteomic profiles of WM cells with that of other LPDs. We were able to demonstrate that WM constitutes a unique proteomic entity as compared with chronic lymphocytic leukemia and marginal zone lymphoma. Statistical comparisons of protein expression levels revealed that a few proteins are distinctly expressed in WM in comparison with other LPDs. In particular we observed a major downregulation of the double strand repair protein Ku70 (XRCC6); confirmed at both the protein and RNA levels in an independent cohort of patients. Hence, we define a distinctive proteomic profile for WM where the downregulation of Ku70-a component of the non homologous end-joining pathway-might be relevant in disease pathophysiology.
authors.affiliation: 1] Laboratoire d'Immunogénétique Moléculaire Humaine, Centre de Recherche d'Immunologie et d'Hématologie. Faculté de Médecine, Université de Strasbourg, Strasbourg Cedex, France [2] Laboratoire Central d'Immunologie, Plateau Technique de Biologie, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg Cedex, France [3] EA RHEM 4369, Laboratoire d'Immunologie, Faculté de médecine, Nancy-Université, Vandœuvre-lès-Nancy, France.
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