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. 2012 Sep 7;2(9):e88.
doi: 10.1038/bcj.2012.35.

Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders

A Perrot  1 , C Pionneau, N Azar, C Baillou, F M Lemoine, V Leblond, H Merle-Béral, M-C Béné, R Herbrecht, S Bahram, L Vallat
Affiliations

Waldenström's macroglobulinemia harbors a unique proteome where Ku70 is severely underexpressed as compared with other B-lymphoproliferative disorders

A Perrot et al. Blood Cancer J. .

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.

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Figures

Figure 1
Figure 1
Principal component analysis (PCA) distinguishes WM, MZL and CLL cells. PCA as a ‘score plot' of a spot map of the 10 protein extracts (3 WM, 3 MZL and 4 CLL) color-coded according to the legend, projected onto the first two principal components. The PC1 and PC2 axes segregate WM samples (pink spots) from both MZL (purple spots) and CLL (blue spots) groups.
Figure 2
Figure 2
2D-E analysis of Ku70 protein expression. Spots were analyzed with Progenesis SameSpots (NonLinear Dynamics). (a) Representative focus of the Ku70 protein (spot no. 712) on WM, MZL and CLL samples 2D-gel images. (b) 3D-representation of the Ku70 volume ratios difference between WM, MZL and CLL samples. (c) Statistical analysis of spot no. 712: significant decrease of Ku70 expression in WM cells as compared with CLL cells (*P<0.05).
Figure 3
Figure 3
Western-blot validation of the Ku70 2D-E profile. Western blot results of Ku70 expression in samples from WM, MZL and CLL cells. Actin was used as loading control.
Figure 4
Figure 4
Quantitative real-time PCR validation for XRCC6. Relative gene-expression quantification for XRCC6 (Ku70) and GUSB (beta-𝒟 glucuronidase) as reference gene, in WM and other B LPD (MZL, MCL and CLL) samples (***P<0.001 by Student's t-test).
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