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Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs

Leukemia volume 29, pages 2270–2273 (2015)Cite this article

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Plasmablastic lymphoma (PBL) is a distinct aggressive B-cell malignancy characterized by a terminally differentiated B-cell phenotype. It usually occurs in immunocompromised patients, either in the setting of HIV infection or in patients with iatrogenic immunosuppression and advanced age.1, 2 Histopathologic features of PBL include immunoblastic and/or plasmablastic morphology, high proliferation rate and immunophenotypic evidence of terminal B-cell differentiation.1, 3 Other features include decreased expression of B-cell lineage antigens4 and frequent infection with Epstein–Barr virus (EBV).5 The molecular and genetic mechanisms underlying its pathogenesis remain largely unknown. Although EBV infection may contribute, it does not account for lymphomagenesis in EBV-negative cases. Among the most frequently detected genomic changes are chromosomal translocations involving the MYC gene, usually in association with the immunoglobulin heavy chain, detected in 49% of cases.6 However, whether MYC translocations represent initiating or late genetic events in PBL pathogenesis is unknown. The limited knowledge of PBL pathogenesis may contribute to the absence of effective targeted therapeutic approaches, and thus to the poor outcome of PBL patients, who have an estimated 2-year overall survival below 40%.1, 7

When clustered hierarchically (Supplementary Methods), samples largely grouped according to histopathologic type, not by primary organ of origin (Figure 1d). The exceptions were four PBLs, two of which (PBL_13 and PBL_15) clustered with EOP and the other two (PBL_6 and PBL_8) clustered with DLBCL. The latter two PBL cases exhibited characteristic PBL morphology with the following immunophenotypes: CD79a+CD138- MUM1+PAX5-CD20-EBER-(PBL_6) and CD79a+CD138+MUM1+PAX5-CD20- EBER+CD10+ (PBL_8) and lacked expression of pan B-cell markers CD20 and PAX5. Overall, gene expression profiles of PBLs were more similar to the EOPs than DLBCLs, likely owing to the origin of both PBLs and EOPs from plasma cells.

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Acknowledgements

ISL is supported by Sylvester Comprehensive Cancer Center and the Dwoskin Family, Recio Family and Anthony Rizzo Family Foundations. AJG is supported by U54CA149145 (NCI Integrative Cancer Biology Program). FV is supported by funds from the Translational Grant of the Leukemia & Lymphoma Society, National Institutes of Health K08 Physician-Scientist Award K08 CA143151-01 and the 2015 CTSI Miami Pilot Award Program.

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  1. J Chapman and A J Gentles: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Hematopathology, Department of Pathology, University of Miami, Miami, FL, USA

    J Chapman, V Sujoy & F Vega

  2. Stanford Center for Cancer Systems Biology, Stanford University, Stanford, CA, USA

    A J Gentles

  3. Virginia Commonwealth University, Richmond, VA, USA

    C I Dumur & T L Blevins

  4. Derpartment of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    L Bernal-Mizrachi

  5. Department of Pathology, Emory School of Medicine, Atlanta, GA, USA

    M Mosunjac

  6. Division of Hematology-Oncology, Department of Medicine, University of Miami and Sylvester Comprehensive Cancer Center, Miami, FL, USA

    A Pimentel, D Zhu & I S Lossos

  7. Department of Molecular and Cellular Pharmacology, University of Miami, Miami, FL, USA

    I S Lossos

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Chapman, J., Gentles, A., Sujoy, V. et al. Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs. Leukemia 29, 2270–2273 (2015). https://doi.org/10.1038/leu.2015.109

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