Transcriptional Analysis of Lennert Lymphoma Reveals a Unique Profile and Identifies Novel Therapeutic Targets.

Maryam Etebari,Giorgio Inghirami,Javeed Iqbal,Pier Paolo Piccaluga,Cristiano Peron,Claudio Agostinelli,Mohsen Navari,Axel Visani

doi:10.3389/fgene.2019.00780

Abstract

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 with 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. Preclinical and clinical studies testing the efficacy of PI3K/MTOR inhibitors in this setting are warranted.

Highlights

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas
More than 25 different entities are currently listed in the World Health Organization (WHO) classification (Swerdlow et al, 2016; Swerdlow et al, 2017), the most common nodal PTCL subtypes include anaplastic large-cell lymphoma ALK+ and ALK, angioimmunoblastic T-cell lymphoma and other T-follicular helper-derived tumors, and peripheral T-cell lymphoma—not
In the fourth edition of the WHO classification, Lennert lymphoma (LL) was classified as a PTCL/NOS morphological variant characterized by clear cell cytology, cytotoxic phenotype, and abundant, when not prominent, epithelioid cells reaction (Swerdlow et al, 2017)

Summary

Introduction

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas. In order to generate gene expression profiles (GEPs), we included all the tumor and 10 normal CD4+ T-cell samples.

Results

Conclusion