Proteomic Analysis of Malignant B-Cell Derived Microparticles Reveals CD148 as a Potentially Useful Antigenic Biomarker for Mantle Cell Lymphoma Diagnosis

The diagnosis of mature B-cell neoplasms (MBCN) remains difficult in a number of cases, especially leukemic phases of non-Hodgkin lymphoma, for which discriminating criteria or biomarker are often lacking. To identify new surface biomarkers, we developed an original proteomic approach based on mass spectrometry analysis of plasma membrane microparticles derived from chronic B-cell lymphoproliferations of single patients: chronic lymphocytic leukemia (CLL), small cell lymphoma (SLL) and mantle cell lymphoma (MCL). A straightforward selection process for proteomic-based candidate biomarker identification was further constructed in order to propose potentially useful and relevant biomarkers. Comparison of the lists of the proteins identified in each pathology combined to highly stringent MS validation criteria for protein identification allowed to propose CD148, a membrane receptor with phosphatase activity, as a discriminating biomarker candidate. Flow cytometry analyses, performed on 158 patients and 30 controls, showed that an anti-CD148 antibody stained significantly higher MCL than CLL and SLL circulating cells (p < 0.0001), which validates CD148 overexpression in MCL. Our results indicate that a medium or high CD148 expression level may exclude the diagnosis of CLL and high CD148 expression levels (CD148 MFI equal or superior to 2 times the value obtained with CLL/SLL) allows MCL diagnosis to be suspected with 91% specificity (versus CLL and SLL) and 78% sensitivity. This study is one of the first where proteomic strategies allowed to identify a potentially useful biomarker.