Uniform expression of Notch1, suppressor of B-cellspecific gene expression, in plasmablastic lymphoma

Context.-Although the loss of B-lineage-specific gene expression is a distinctive feature of plasmablastic lymphoma, the underlying mechanism remains poorly understood. A candidate for this mechanism is Notch 1 signaling, which interferes with the activity of B-cell-specific transcription factors E2A and early B-cell factor and positively regulates the mammalian target of rapamycin (mTOR) pathway. Objective.-To explore the mechanism of loss of B-cell phenotype by correlating expression of B-cell markers with that of Notch1 and downstream targets of the mTOR pathway in plasmablastic lymphoma. Design.-A combination of flow cytometric and immunohistochemical immunophenotyping techniques was used on 9 cases of plasmablastic lymphoma to correlate loss of B-cell markers with expression of Notch1 and downstream activation of the mTOR pathway. These results are compared with 5 cases of primary effusion lymphoma and 21 cases of plasma cell myeloma. Results.-Plasmablastic lymphoma cases exhibit nearly complete loss of B-cell-associated markers and uniform expression of Notchl, with a predominantly nuclear staining pattern. There is a concurrent activation of the mTOR pathway, indicated by expression of mTOR targets eukaryotic initiation factor 4E-binding protein 1 and phosphorylated ribosomal protein S6 in most cases. Similar results are seen in cases of primary effusion lymphoma and plasma cell myeloma. Conclusions.-These findings suggest that activation of Notch1 may be involved in suppression of B-cellspecific gene expression and global loss of the B-cell phenotype in plasmablastic lymphoma, similar to primary effusion lymphoma and plasma cell myeloma. Thus, there might be a role for the Notch1 and mTOR pathways in the pathogenesis and therapy of plasmablastic lymphoma.