当前位置: X-MOL 学术J. Pathol. › 论文详情
Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell.
The Journal of Pathology ( IF 5.979 ) Pub Date : 2019-12-20 , DOI: 10.1002/path.5376
Wen-Qing Yao,Fangtian Wu,Wenyan Zhang,Shih-Sung Chuang,Joe S Thompson,Zi Chen,Shao-Wei Zhang,Alexandra Clipson,Ming Wang,Hongxiang Liu,Hani Bibawi,Yuanxue Huang,Luis Campos,John W Grant,Penny Wright,Hesham Ei-Daly,Lívia Rásó-Barnett,Lorant Farkas,George A Follows,Zifen Gao,Ayoma D Attygalle,Margaret Ashton-Key,Weiping Liu,Ming-Qing Du

Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor β (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
更新日期:2020-01-17

 

全部期刊列表>>
物理学研究前沿热点精选期刊推荐
chemistry
自然职位线上招聘会
欢迎报名注册2020量子在线大会
化学领域亟待解决的问题
材料学研究精选新
GIANT
ACS ES&T Engineering
ACS ES&T Water
ACS Publications填问卷
屿渡论文,编辑服务
阿拉丁试剂right
南昌大学
王辉
南方科技大学
彭小水
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
天合科研
x-mol收录
X-MOL
苏州大学
廖矿标
深圳湾
试剂库存
down
wechat
bug