التفاصيل البيبلوغرافية
| العنوان: |
Angioimmunoblastic T‐cell lymphoma contains multiple clonal T‐cell populations derived from a common TET2 mutant progenitor cell |
| المؤلفون: |
Yao, Wen‐Qing, Wu, Fangtian, Zhang, Wenyan, Chuang, Shih‐Sung, Thompson, Joe S, Chen, Zi, Zhang, Shao‐Wei, Clipson, Alexandra, Wang, Ming, Liu, Hongxiang, Bibawi, Hani, Huang, Yuanxue, Campos, Luis, Grant, John W, Wright, Penny, EI‐Daly, Hesham, Rásó‐Barnett, Lívia, Farkas, Lorant, Follows, George A, Gao, Zifen, Attygalle, Ayoma D, Ashton‐Key, Margaret, Liu, Weiping, Du, Ming‐Qing |
| المساهمون: |
Bloodwise, Pathological Society of Great Britain and Ireland |
| المصدر: |
The Journal of Pathology ; volume 250, issue 3, page 346-357 ; ISSN 0022-3417 1096-9896 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2020 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
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 ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/path.5376 |
| الإتاحة: |
https://doi.org/10.1002/path.5376Test |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.B3B140E8 |
| قاعدة البيانات: |
BASE |
