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A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling

Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequen...

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Autores principales: Zhang, Yang, Wang, Zhihua, Hu, Guoyu, Li, Jieping, Chen, Yongheng, Jiang, Yi, Zhong, Haiying, Liu, Xianling, Hu, Chunhong, Peng, Honglin, Xu, Yunxiao, Cheng, Zhao, Zhang, Guangsen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539911/
https://www.ncbi.nlm.nih.gov/pubmed/36212426
http://dx.doi.org/10.3389/fonc.2022.870676
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author Zhang, Yang
Wang, Zhihua
Hu, Guoyu
Li, Jieping
Chen, Yongheng
Jiang, Yi
Zhong, Haiying
Liu, Xianling
Hu, Chunhong
Peng, Honglin
Xu, Yunxiao
Cheng, Zhao
Zhang, Guangsen
author_facet Zhang, Yang
Wang, Zhihua
Hu, Guoyu
Li, Jieping
Chen, Yongheng
Jiang, Yi
Zhong, Haiying
Liu, Xianling
Hu, Chunhong
Peng, Honglin
Xu, Yunxiao
Cheng, Zhao
Zhang, Guangsen
author_sort Zhang, Yang
collection PubMed
description Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A>G (p.Tyr82Cys) and c.265C>T(p.Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH.
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spelling pubmed-95399112022-10-08 A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling Zhang, Yang Wang, Zhihua Hu, Guoyu Li, Jieping Chen, Yongheng Jiang, Yi Zhong, Haiying Liu, Xianling Hu, Chunhong Peng, Honglin Xu, Yunxiao Cheng, Zhao Zhang, Guangsen Front Oncol Oncology Recently, it have been reported that Hepatitis A Virus-Cellular Receptor 2(HAVCR2,encoding T-cell immunoglobulin and Mucin-Containing Protein 3[TIM3]) mutations are associated with severe hemophagocytic syndrome(HLH) in subcutaneous panniculitis-like T-cell lymphoma(SPTCL),and there are also frequent mutations in sporadic SPTCL, suggesting the individuals harboring HAVCR2(TIM-3) germline mutations are highly susceptible to familial or sporadic SPTCL. Here, we identify a novel germline compound heterozygous mutation of TIM-3 gene,c.245A>G (p.Tyr82Cys) and c.265C>T(p.Arg89Cys) variations in a single familial case with EBV-positive peripheral T-cell lymphoma(NOS),accompanied HLH;we also detected Tyr82Cys germline mutation in TIM-3 gene in one sporadic patient with cutaneous T cell lymphoma. We screened the distributive frequencies for TIM-3 mutations in healthy controls(n=87), B-(n=79) or T-cell lymphoma(n=25) not SPTCL, and the results showed that the mutation was found in two out of 25 patients with T-cell lymphoma but was not detected in 79 patients with B-cell lymphoma nor in a group of 87 controls. The mRNA expression of TIM-3 on primary cells and transfected HEK293 cells reduced significantly, indicating Tyr82Cys and Arg89Cys mutations is a loss-of function mutations on TIM-3,resulting in a weakened TIM-3 signaling. Our results suggest Tyr82Cys TIM-3 germline mutations are not only limited in SPTCL, and also occurred in other types of T-cell lymphoma, especially complicated HLH. TIM-3 mutations may be an predisposing factor for T-cell lymphoma and molecular marker for auxiliary diagnosis in T cell lymphoma,especially complicated with HLH. Frontiers Media S.A. 2022-09-23 /pmc/articles/PMC9539911/ /pubmed/36212426 http://dx.doi.org/10.3389/fonc.2022.870676 Text en Copyright © 2022 Zhang, Wang, Hu, Li, Chen, Jiang, Zhong, Liu, Hu, Peng, Xu, Cheng and Zhang https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Oncology
Zhang, Yang
Wang, Zhihua
Hu, Guoyu
Li, Jieping
Chen, Yongheng
Jiang, Yi
Zhong, Haiying
Liu, Xianling
Hu, Chunhong
Peng, Honglin
Xu, Yunxiao
Cheng, Zhao
Zhang, Guangsen
A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title_full A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title_fullStr A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title_full_unstemmed A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title_short A novel germline HAVCR2 (TIM-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in EBV-positive peripheral T-cell lymphoma (NOS) with down-regulated TIM-3 signaling
title_sort novel germline havcr2 (tim-3) compound heterozygous mutation is related to hemophagocytic lymphohistiocytic syndrome in ebv-positive peripheral t-cell lymphoma (nos) with down-regulated tim-3 signaling
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9539911/
https://www.ncbi.nlm.nih.gov/pubmed/36212426
http://dx.doi.org/10.3389/fonc.2022.870676
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