Total proteome analysis identifies migration defects as a major pathogenetic factor in immunoglobulin heavy chain variable region (IGHV)-unmutated chronic lymphocytic leukemia.
Bottom Line: Furthermore, UM-CLL cells underexpressed proteins associated with cytoskeletal remodeling and overexpressed proteins associated with transcriptional and translational activity.Taken together, our findings indicate that UM-CLL cells are less migratory and more adhesive than M-CLL cells, resulting in their retention in lymph nodes, where they are exposed to proliferative stimuli.Our study illustrates the potential of total proteome analysis to elucidate pathogenetic mechanisms in cancer.
Affiliation: From the ‡Department of Molecular and Clinical Cancer Medicine.Show MeSH
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Mentions: We next used GeneGo pathway maps from MetaCore to identify pathways enriched by the 274 proteins that were differentially expressed in the two subsets of CLL samples (p < 0.05). The enrichment analysis identified 169 signaling pathways (p < 0.05) (supplemental Table S3). Remarkably, 26 of the top 50 most significantly altered pathways were associated with cell migration/adhesion. In total, 43 cell migration/adhesion pathways (Table 2) were significantly enriched by 39 differentially expressed proteins (Table 3). As all of these 39 proteins were involved in lymphocyte entry into, transit within, or exit from the lymphoid tissues (Fig. 2) and 35 of them were expressed at significantly lower levels in UM-CLL samples, these results suggest that UM-CLL cells have reduced migratory properties compared with their M-CLL counterparts.
Affiliation: From the ‡Department of Molecular and Clinical Cancer Medicine.