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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.00780

Transcriptional analysis of Lennert lymphoma reveals a unique profile and identifies novel therapeutic targets

Maryam Etebari1, 2, 3,  MOHSENohsen Navari2, 3, 4, Claudio Agostinelli1, Axel Visani1, Cristiano Peron1,  Javeed Iqbal5, Giorgio Inghirami6 and  Pier Paolo Piccaluga1, 7, 8*
  • 1Department of Diagnostic and Experimental Medicine, University of Bologna, Italy
  • 2Department of Medical Biotechnology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Iran
  • 3Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Iran
  • 4Bioinformatics Research Group, Mashhad University of Medical Sciences, Iran
  • 5Department of Pathology and Microbiology, College of Medicine, University of Nebraska Medical Center, United States
  • 6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, United States
  • 7Euro-Mediterranean Institute of Science and Technology (IEMEST), Italy
  • 8Department of Human Pathology, School of Medicine, Jomo Kenyatta University of Agriculture and Technology, Kenya

Lennert lymphoma (LL) is a lymphoepithelioid morphological variant of peripheral T-cell lymphoma/not otherwise specified (PTCL/NOS), clinically characterized by better prognosis if compared to other PTCL/NOS. Although well characterized as far as morphology and phenotype are concerned, very little is known regarding its molecular features.
In this study we investigated the transcriptional profile of this tumor aiming 1) to identify its cellular counterparts; 2) to better define its relation with other PTCLs – and therefore its possible position in lymphoma classification; and 3) to define pathogenetic mechanisms, possibly unveiling novel therapeutic targets. To address these issues we performed gene and microRNA expression profiling on LL and other PTCL/NOS cases; we identified different genes and microRNAs that discriminated LL from other PTCL/NOS. Particularly, LL revealed a molecular signature significantly enriched in helper function and clearly distinguishable from other PTCL/NOS. Furthermore, PI3K/Akt/mTOR pathway emerged as novel potential therapeutic target.
In conclusion, based on the already known particular morphological and clinical features, the new molecular findings support the hypothesis that LL might be classified as a separate entity. Pre-clinical and clinical studies testing the efficacy of PI3K/MTOR inhibitors in this setting are warranted.

Keywords: Lennert's lymphoma, Peripheral T-Cell lymphoma-not otherwise specified (PTCL-NOS), WHO classification, Gene expression profiling (GEP), miRNA profiling

Received: 19 Feb 2019; Accepted: 23 Jul 2019.

Edited by:

Rengyun Liu, School of Medicine, Johns Hopkins University, United States

Reviewed by:

Kartiki V. Desai, National Institute of Biomedical Genomics (NIBMG), India
Shicheng Guo, Marshfield Clinic Research Institute, United States  

Copyright: © 2019 Etebari, Navari, Agostinelli, Visani, Peron, Iqbal, Inghirami and Piccaluga. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Pier Paolo Piccaluga, Department of Diagnostic and Experimental Medicine, University of Bologna, Bologna, Italy, pierpaolo.piccaluga@unibo.it