Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma

Xie, Caiqin; Li, Xian; Zeng, Hui; Han, Weidong

doi:10.1186/s40164-020-00188-w

Cited by 22 publications

(27 citation statements)

References 119 publications

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“…As reported in other studies, the representative genetic alterations to induce a robust T follicular helper phenotype ( RHOA, IDH2, and DNMT3A ) of AITL also appeared in other TFH lymphomas [ 24 ]. However, other mutation profiles that play an essential role in T-cell receptor (TCR) signaling, transcription factors, and tumor suppressors were shared evenly between AITL, other TFH lymphomas, and PTCL-NOS [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

et al. 2021

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Background The 2016 World Health Organization (WHO) classification introduced nodal lymphomas of T follicular helper (Tfh) cell origin, such as angioimmunoblastic T-cell lymphoma (AITL), follicular peripheral T-cell lymphoma (F-PTCL), and nodal peripheral T-cell lymphoma with T follicular helper phenotype (nodal PTCL with TFH phenotype). However, the accurate incidence rate and clinical characteristics of F-PTCL and nodal PTCL with TFH are unstudied. Methods Between February 2012 to June 2020, a total of 207 cases diagnosed with nodal lymphomas of T follicular helper (Tfh) cell origin and PTCL-NOS were reviewed for clinical and histopathologic data. PTCL-NOS was defined to not correlate to any of the specific entities of mature T cell lymphoma in the WHO 2016 classification. We attempted to classify PTCL-GATA3 and PTCL-TBX21 by IHC staining. Target gene analysis was performed on a few patients with sufficient blood and tissue samples additionally. Results Among 207 patients, 111 patients (53.6%) had AITL, 67 patients (32.4%) had PTCL-NOS, 19 patients (9.2%) had F-PTCL, and 10 patients (4.8%) had nodal PTCL with TFH phenotype. We re-defined and analyzed F-PTCL and nodal PTCL with TFH phenotype into other TFH lymphomas. AITL (N = 101/111, 91.0%) was found to have a higher frequency of stage III/IV cancers compared to other TFH lymphomas (N = 22/29, 75.0%) and PTCL-NOS (N = 53/67, 79.1%; p-value = 0.03). The OS of AITL and other TFH lymphomas was similarly superior to PTCL-NOS (p-value = 0.02). AITL and other TFH lymphomas showed the TBX21 subtype more commonly than the GATA3 subtype. Mutations related to the RAS family (RHOA) and those related to epigenetic regulators (IDH2, DNMT3A, and TET2) were shown mainly in AITL and other TFH lymphomas. Conclusions Other TFH lymphomas appear to be a rare disease entity around one-quarter in nodal lymphomas of T follicular helper (Tfh) cell origin. Their less aggressive clinical feature than we did not expect is utterly different from PTCL-NOS and AITL. On the other hand, other TFH lymphomas share some characteristics, such as the cell of origin, a more common TBX21 subtype, and genetic variation such as RAS family mutation and epigenetic regulators, with AITL.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

et al. 2021

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“…HOXA1 activates nuclear factor κ‐light‐chain‐enhancer of activated B cells (NF‐κB) to modulate the tumour necrosis factor‐α/NF‐κB signalling pathway 46 or regulates tumour progression in gastric cancer via cyclin D1 45 . The deletion of CDKN2A was reported in some adult PTCL, 11–13 while our observations indicated that it is limited to EBV – PTCL [PTCL‐NOS and subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL)], but not EBV + PTCL, in paediatric PTCL.…”

Section: Discussionmentioning

confidence: 70%

“…To refine the classification of PTCL even more, further clarification of the molecular pathogenesis will be required 11–14 . A subset of PTCL‐NOS shares some of the recurrent genetic alterations found in angioimmunoblastic T‐cell lymphoma (AITL), such as mutations affecting ten–eleven translocation methylcytosine dioxygenase 2 ( TET2 ), DNA methyltransferase 3α ( DNMT3A ) and Ras homolog family member A ( RHOA ), 15 and has been recommended to be classified as PTCL‐NOS with a T‐follicular helper (TFH) cell phenotype as a provisional entity (TFH PTCL‐NOS) in the revised WHO classification 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Characteristics of genetic alterations of peripheral T‐cell lymphoma in childhood including identification of novel fusion genes: the Japan Children’s Cancer Group (JCCG)

et al. 2021

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Summary Peripheral T‐cell lymphoma (PTCL) is a group of heterogeneous non‐Hodgkin lymphomas showing a mature T‐cell or natural killer cell phenotype, but its molecular abnormalities in paediatric patients remain unclear. By employing next‐generation sequencing and multiplex ligation‐dependent probe amplification of tumour samples from 26 patients, we identified somatic alterations in paediatric PTCL including Epstein–Barr virus (EBV)‐negative (EBV–) and EBV‐positive (EBV+) patients. As recurrent mutational targets for PTCL, we identified several previously unreported genes, including TNS1, ZFHX3, LRP2, NCOA2 and HOXA1, as well as genes previously reported in adult patients, e.g. TET2, CDKN2A, STAT3 and TP53. However, for other reported mutations, VAV1‐related abnormalities were absent and mutations of NRAS, GATA3 and JAK3 showed a low frequency in our cohort. Concerning the association of EBV infection, two novel fusion genes: STAG2‐AFF2 and ITPR2‐FSTL4, and deletion and alteration of CDKN2A/2B, LMO1 and HOXA1 were identified in EBV– PTCL, but not in EBV+ PTCL. Conversely, alterations of PCDHGA4, ADAR, CUL9 and TP53 were identified only in EBV+ PTCL. Our observations suggest a clear difference in the molecular mechanism of onset between paediatric and adult PTCL and a difference in the characteristics of genetic alterations between EBV– and EBV+ paediatric PTCL.

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“…AITL is a special subtype of peripheral T-cell lymphoma that originates from follicular helper T cells (TFH), often with fever, night sweats, weight loss, lymphadenopathy, skin rash, and other clinical manifestations 3 Skin involvement is one of the most common extranodal manifestations of the disease 4 Due to the heterogeneity of AITL, most cases do not get diagnosed until weeks or months after the onset of symptoms.…”

Section: Discussionmentioning

confidence: 99%

Angioimmunoblastic T-cell lymphoma combined with Hodgkin’s lymphoma:a case report

Gao

Kang

et al. 2021

Preprint

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Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma

Cited by 22 publications

References 119 publications

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas

Characteristics of genetic alterations of peripheral T‐cell lymphoma in childhood including identification of novel fusion genes: the Japan Children’s Cancer Group (JCCG)

Angioimmunoblastic T-cell lymphoma combined with Hodgkin’s lymphoma:a case report

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