Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes

Pier Paolo Piccaluga, Giulia De Falco, Manjunath Kustagi, Anna Gazzola, Claudio Agostinelli, Claudio Tripodo, Eleonora Leucci, Anna Onnis, Annalisa Astolfi, Maria Rosaria Sapienza, Cristiana Bellan, Stefano Lazzi, Lynnette Tumwine, Michael Mawanda, Martin Ogwang, Valeria Calbi, Serena Formica, Andrea Califano, Stefano A. Pileri, Lorenzo Leoncini

Research output: Contribution to journalArticle

Abstract

Burkitt lymphoma (BL) is classified into 3 clinical subsets: endemic, sporadic, and immunodeficiency-associated BL. So far, possible differences in their gene expression profiles (GEPs) have not been investigated. We studied GEPs of BL subtypes, other B-cell lymphomas, and B lymphocytes; first, we found that BL is a unique molecular entity, distinct from other B-cell malignancies. Indeed, by unsupervised analysis all BLs clearly clustered apart of other lymphomas. Second, we found that BL subtypes presented slight differences in GEPs. Particularly, they differed for genes involved in cell cycle control, B-cell receptor signaling, and tumor necrosis factor/nuclear factor κB pathways. Notably, by reverse engineering, we found that endemic and sporadic BLs diverged for genes dependent on RBL2 activity. Furthermore, we found that all BLs were intimately related to germinal center cells, differing from them for molecules involved in cell proliferation, immune response, and signal transduction. Finally, to validate GEP, we applied immunohistochemistry to a large panel of cases and showed that RBL2 can cooperate with MYC in inducing a neoplastic phenotype in vitro and in vivo. In conclusion, our study provided substantial insights on the pathobiology of BLs, by offering novel evidences that may be relevant for its classification and possibly future treatment.

Original languageEnglish
Pages (from-to)3596-3608
Number of pages13
JournalBlood
Volume117
Issue number13
DOIs
Publication statusPublished - Mar 31 2011

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ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Piccaluga, P. P., De Falco, G., Kustagi, M., Gazzola, A., Agostinelli, C., Tripodo, C., Leucci, E., Onnis, A., Astolfi, A., Sapienza, M. R., Bellan, C., Lazzi, S., Tumwine, L., Mawanda, M., Ogwang, M., Calbi, V., Formica, S., Califano, A., Pileri, S. A., & Leoncini, L. (2011). Gene expression analysis uncovers similarity and differences among Burkitt lymphoma subtypes. Blood, 117(13), 3596-3608. https://doi.org/10.1182/blood-2010-08-301556