Low miR-214-5p Expression Correlates With Aggressive Subtypes of Pediatric ALCL With Non-Common Histology.

Piero Di Battista,Federica Lovisa,Carlotta C Damanti,Angelo Paolo Dei Tos,Lara Mussolin,Lavinia Ferrone,Enrico Gaffo,Elisa Carraro,Vincenza Guzzardo,Anna Garbin,Luca Lo Nigro,Marco Pizzi,Stefania Bortoluzzi,Alessandra Biffi,Marta Pillon,Rossella Mura,Ilaria Gallingani

doi:10.3389/fonc.2021.663221

Abstract

The unsatisfactory cure rate of relapsing ALK-positive Anaplastic Large-Cell Lymphoma (ALCL) of childhood calls for the identification of new prognostic markers. Here, the small RNA landscape of pediatric ALK-positive ALCL was defined by RNA sequencing. Overall, 121 miRNAs were significantly dysregulated in ALCL compared to non-neoplastic lymph nodes. The most up-regulated miRNA was miR-21-5p, whereas miR-19a-3p and miR-214-5p were reduced in ALCL. Characterization of miRNA expression in cases that relapsed after first line therapy disclosed a significant association between miR-214-5p down-regulation and aggressive non-common histology. Our results suggest that miR-214-5p level may help to refine the prognostic stratification of pediatric ALK-positive ALCL.

Highlights

Anaplastic Large-Cell Lymphoma (ALCL) accounts for 10-15% of pediatric and adolescent nonHodgkin lymphomas
This study associates the risk of relapse in pediatric ALCL with miRNA signatures and identifies miRNA expression patterns related to high risk NC histotypes
Low miR-214-5p expression is associated with poor prognosis in other solid tumors [12, 13], whereas high miR-214-5p expression with good outcome in diffuse large B-cell lymphoma [14]

Summary

INTRODUCTION

Anaplastic Large-Cell Lymphoma (ALCL) accounts for 10-15% of pediatric and adolescent nonHodgkin lymphomas. MiR-19a-3p significantly downregulated in ALCL compared to RLN (Figure 1) was demonstrated to be significantly reduced in comparison to activated T-cells (Mann Whitney, p-value = 0.047; Supplementary Figure 3B), suggesting that miR-19a-3p could play a tumor suppressor role in ALCL, in line with recent data in invasive breast cancer [10]. Compared to common type ALCL (CM), cases with NC histology disclosed significantly lower expression of miR-2145p (Mann Whitney, p-value = 0.046; Figure 2). This observation was confirmed by in situ hybridization for miR-214-5p on representative tissue sections from ALCL cases with CM (n = 6) and NC (n = 6; 4 lympho-histiocytic and 2 small cell) histology. Estimating miR-214-5p expression level by qRTPCR and miRNA in situ hybridization [11] could prove useful to complement the standard histopathological evaluation of pediatric ALK-positive ALCL at diagnosis

DISCUSSION

Findings

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