HLA-G+3027 polymorphism is associated with tumor relapse in pediatric Hodgkin's lymphoma.

Valli De Re,Lia Martina,Paola Muggeo,Alessandra Sala,Caterina Elia,Salvatore Buffardi,Piero Farruggia,Mariangela De Zorzi,Marta Pillon,Luciana Vinti,Lara Mussolin,Barbara Famengo,Maurizio Bianchi,Edgardo D Carosella,Roberta Burnelli,Laura Caggiari,Nicola Santoro,Maurizio Mascarin,Emanuele Stefano D’Amore

doi:10.18632/oncotarget.22515

Abstract

In this study, we tested whether polymorphisms in human leukocyte antigen G (HLA-G) were associated with event-free survival (EFS) in pediatric Hodgkin's lymphoma (HL). We evaluated the association of HLA-G 3′-UTR polymorphisms with EFS in 113 pediatric HL patients treated using the AIEOP LH-2004 protocol. Patients with the +3027-C/A genotype (rs17179101, UTR-7 haplotype) showed lower EFS than those with the +3027-C/C genotype (HR= 3.23, 95%CI: 0.99-10.54, P=0.012). Female patients and systemic B symptomatic patients with the HLA-G +3027 polymorphism showed lower EFS. Multivariate analysis showed that the +3027-A polymorphism (HR 3.17, 95%CI 1.16-8.66, P=0.025) was an independent prognostic factor. Immunohistochemical analysis showed that HL cells from patients with the +3027-C/A genotype did not express HLA-G. Moreover, HLA-G +3027 polymorphism improved EFS prediction when added to the algorithm for therapeutic group classification of pediatric HL patients. Our findings suggest HLA-G +3027 polymorphism is a prognostic marker in pediatric HL patients undergoing treatment according to LH-2004 protocol.

Highlights

Hodgkin lymphoma (HL) originates mostly from transformed B-lymphocytes and represents 6% of the childhood tumors [1]
We showed that the +3027-A (UTR-7 haplotype) human leukocyte antigen G (HLA-G) polymorphism was associated with a low event-free survival (EFS) in pediatric Hodgkin’s lymphoma (HL) patients treated according to the AIEOP LH-2004 protocol, more evident in female gender www.impactjournals.com/oncotarget and patients with systemic B symptoms
We demonstrated that histocompatibility leukocyte antigen (HLA)-G was not expressed in the tumor cells of HL patients with +3027-C/A genotype and present only in a minority of cases (20%) with the wild type +3027-C/C genotype

Summary

Introduction

Hodgkin lymphoma (HL) originates mostly from transformed B-lymphocytes and represents 6% of the childhood tumors [1]. Mononuclear Hodgkin (H) and multinucleated Reed-Sternberg (HRS) tumor cells represent 0.1%–2% of the total tumor infiltrating cells [2]. It is important to identify markers that predict relapse in HL patients in order to obtain better responses with less aggressive therapy, considering the long term adverse effects of HL therapy such as secondary cancer, infertility and neurological toxicity [5]. It is key to identify genetic factors that are involved in HL pathogenesis and response to therapy [6,7]

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Results

Conclusion