Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma

Luca Agnelli, Elisabetta Mereu, Elisa Pellegrino, Tania Limongi, Ivo Kwee, Elisa Bergaggio, Maurilio Ponzoni, Alberto Zamò, Javeed Iqbal, Pier Paolo Piccaluga, Antonino Neri, Wing C. Chan, Stefano Pileri, Francesco Bertoni, Giorgio Inghirami, Roberto Piva

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Anaplastic large-cell lymphomas (ALCLs) are a group of clinically and biologically heterogeneous diseases including the ALK+ and ALK+ systemic forms. Whereas ALK+ ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK- ALCL are missing, and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial. In the present study, we undertook a transcriptional profiling meta-analysis of 309 cases, including ALCL and other primary T-NHL samples. Pathway discovery and prediction analyses defined a minimum set of genes capable of recognizing ALK- ALCL. Application of quantitative RT-PCR in independent datasets from cryopreserved and formalin-fixed paraffin-embedded samples validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK- ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. In conclusion, our data justify the possibility of translating quantitative RT-PCR protocols to routine clinical settings as a new approach to objectively dissect T-NHL and to select more appropriate therapeutic protocols.

Original languageEnglish (US)
Pages (from-to)1274-1281
Number of pages8
JournalBlood
Volume120
Issue number6
DOIs
StatePublished - Aug 9 2012

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Agnelli, L., Mereu, E., Pellegrino, E., Limongi, T., Kwee, I., Bergaggio, E., Ponzoni, M., Zamò, A., Iqbal, J., Piccaluga, P. P., Neri, A., Chan, W. C., Pileri, S., Bertoni, F., Inghirami, G., & Piva, R. (2012). Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic large-cell lymphoma. Blood, 120(6), 1274-1281. https://doi.org/10.1182/blood-2012-01-405555