Table 1.
Molecular characterization of the main non-cutaneous PTCL entities.
| Entity | Differentiation | Molecular features |
|---|---|---|
| TFH-lymphomas | TFH | - DNA methylation: TET2, DNMT3A, IDH2 R172 mutations - TCR pathway: RHOA G17V, CD28, VAV1, PLCG1 mutations - Fusion transcripts: ICOS_CD28, CTLA4_CD28, ITK_SYK, ITK_FER, fusion transcripts involving VAV1 |
| ALK-positive ALCL | Activated cytotoxic T cell | - Fusion transcripts involving ALK
- Mutations in genes of the NOTCH1 pathway |
| ALK-negative ALCL | Activated cytotoxic T cell |
STAT3 activation: JAK1 and/or STAT3 mutations Fusion transcripts involving ROS, TYK2, FRK, CAPRIN2 Absence of STAT3 activation: DUSP22/IRF4 (locus 6p25.3) rearrangement MSCE116K mutation Others: TP63 rearrangements |
| Breast-implant ALCL | Activated cytotoxic T cell | - JAK/STAT pathway: STAT3, JAK1, SOCS3, STAT5B, SOCS1, PTPN1 mutations - Epigenetics: KMT2D, KMT2C, CREBBP, CHD2, TET2, DNMT3A mutations |
| ATLL | Memory regulator T cell |
- TCR pathway: PLCG1, PRKCB, CARD11, VAV1, IRF4, FYN, CCR4, CCR7, RHOA, CD28 mutations - Immunosurveillance: CD58, B2M, HLA (class I) mutations - JAK/STAT pathway: JAK3, STAT3, PTPN1 mutations - Transcription factor: GATA3, IKZF2, PRDM1 mutations - Epigenetics: TET2, DNMT3A, IDH2, SETD2, EP300, KDM6A mutations - Fusion transcripts: ICOS_CD28 and/or CTLA4_CD28 |
| ENKTCL (nasal type) | NK>>T (γδ or αβ) | - BCOR, DDX3X, TP53, MGA, STAT3, STAT5B, MLL2, ARID1A, MSN mutations - 3 molecular subgroups : °TSIM : mutations of genes of the JAK/STAT pathway, TP53, amp9p24.1(JAK2, PDL1/2), amp17q21.2 (STAT3/5A/5B), EBV latency type II => NK cells °HEA: mutations of HDAC9, EP300, ARID1A, EBV latency type II => T-cells °MB: mutations of MGA, del1p22.1 (BRDT), MYC overexpression, EBV latency type I => T-cells |
| HSTL | Tgδ> Tαβ | - SETD2, STAT5B, INO80, ARID1B, STAT3, PIK3CD mutations |
| Indolent clonal T-cell lymphoproliferative disorder of the gastro-intestinal tract | CD8+ or CD4-/CD8- (TH2) | - Structural alterations of the 3’UTR regions of IL2 coding gene |
| CD4+ or CD4+/CD8+ | - JAK/STAT pathway: STAT3, SOCS1 mutations, STAT3_JAK2 fusion - Epigenetics: TET2, DNMT3A, KMT2D mutations |
|
| EATL | Intraepithelial lymphocyte (Tαβ) |
- JAK/STAT pathway: JAK1 (p.G1097 dans 50%), JAK3, STAT3, STAT5B, SOCS1 mutations - KRAS, NRAS mutations - NFκB pathway: TNFAIP3, TNIP3 mutations - Epigenetics: TET2, KMT2D, DDX3X, SETD2 (15%) mutations |
| MEITL | Intraepithelial lymphocyte (Tγδ > Tαβ) | - Alterations of SETD2 (mutations, deletions) - STAT5B, JAK3, TP53, GNAI2 mutations |
| T-LGLL | Tαβ (CD8) >> Tγδ |
- JAK/STAT pathway: STAT3, less frequently STAT5B mutations - Epigenetics: TET2, DNMT3A |
| PTCL-NOS | TH1 (αβ >> δγ), common cytotoxic phenotype | - Epigenetic: TET2, DNMT3A, KMT2D, SETD2 mutations - TCR pathway: VAV1, PLCG1, PRKCB, CARD11 mutations; fusion transcripts involving VAV1 - JAK/STAT pathway: STAT3, STAT5B, JAK3, SOCS1 mutations |
| TH2 (Tαβ) | - Deletions of CDKN2A, TP53, PDGFA, STK11, WDR24, CDK4, CCND1, AKT, RPTOR… - Gains/amplifications of STAT3, CMYC |
TFH, T follicular helper; ALCL, anaplastic large cell lymphoma; PTCL-NOS, peripheral T-cell lymphoma, not otherwise specified; ATLL, adult T-cell leukemia/lymphoma; ENKTCL: extra-nodal NK/T-cell lymphoma, HSTL, hepatosplenic T-cell lymphoma; EATL, enteropathy associated T-cell lymphoma; MEITL, monomorphic epitheliotropic intestinal T-cell lymphoma; T-LGLL, T-cell large granular lymphocytic leukemia.