mature T-cell and NK-cell non-Hodgkin lymphoma

Summary

mature T-cell and NK-cell non-Hodgkin lymphoma (MONDO:0000430) is a cancer (an umbrella term covering 8 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver) and 290 clinical trials. Top therapeutic interventions include romidepsin, pralatrexate, and belinostat.

At a glance

• Classification: Cancer
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 1
• Clinical trials: 290

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mature T-cell and NK-cell non-Hodgkin lymphoma
Mondo ID	MONDO:0000430
MeSH	D016411
DOID	DOID:0050743, DOID:0050749
ICD-10-CM	C84.4
NCIT	C3468
SNOMED CT	109977009
UMLS	C5551485
MedGen	1790498
GARD	0007368
Is cancer (heuristic)	yes

Also known as: mature T-and NK-cell lymphoma · mature T-cell and NK-cell lymphoma · mature T-cell and NK-cell non-Hodgkin lymphoma · mature T-cell and NK-cell non-Hodgkin’s lymphoma · mature T-cell lymphoma · mature T-cell non-Hodgkin’s lymphoma · peripheral T-cell lymphoma · PTCL

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › hematopoietic and lymphoid system neoplasm › hematopoietic and lymphoid cell neoplasm › lymphoid neoplasm › T-cell and NK-cell neoplasm › neoplasm of mature T-cells or NK-cells › mature T-cell and NK-cell non-Hodgkin lymphoma

Related subtypes (3): chronic lymphoproliferative disorder of NK-cells, peripheral T-cell lymphoma, not otherwise specified, EBV-positive T-cell lymphoproliferative disorder of childhood

Subtypes (8): angioimmunoblastic T-cell lymphoma, systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood, hydroa vacciniforme-like lymphoma, T-cell prolymphocytic leukemia, T-cell large granular lymphocyte leukemia, aggressive NK-cell leukemia, anaplastic large cell lymphoma, breast implant-associated anaplastic large cell lymphoma

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
IDH2	Act	AML,BLCA,CHOL,LGGNOS,OS	CIViC #27

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IDH2	Orphanet:163634	Maffucci syndrome
IDH2	Orphanet:251589	Anaplastic astrocytoma
IDH2	Orphanet:251598	Protoplasmic astrocytoma
IDH2	Orphanet:251601	Fibrillary astrocytoma
IDH2	Orphanet:251604	Gemistocytic astrocytoma
IDH2	Orphanet:251627	Oligodendroglioma
IDH2	Orphanet:251630	Anaplastic oligodendroglioma
IDH2	Orphanet:251656	Oligoastrocytoma
IDH2	Orphanet:251663	Anaplastic oligoastrocytoma
IDH2	Orphanet:296	Ollier disease
IDH2	Orphanet:79315	D-2-hydroxyglutaric aciduria
IDH2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
IDH2	HGNC:5383	ENSG00000182054	P48735	Isocitrate dehydrogenase [NADP], mitochondrial	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IDH2	Isocitrate dehydrogenase [NADP], mitochondrial	Plays a role in intermediary metabolism and energy production.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IDH2	Enzyme (other)	yes	1.1.1.42	Isocitrate_DH_NADP, IsoCit/isopropylmalate_DH_CS, IsoPropMal-DH-like_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IDH2	292	ubiquitous	marker	apex of heart, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IDH2	4,912

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IDH2	P48735	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Maturation of TCA enzymes and regulation of TCA cycle	1	571.0×	0.005	IDH2
Citric acid cycle (TCA cycle)	1	423.0×	0.005	IDH2
Transcriptional activation of mitochondrial biogenesis	1	203.9×	0.007	IDH2
Mitochondrial protein degradation	1	114.2×	0.009	IDH2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glyoxylate cycle	1	8426.0×	4e-04	IDH2
negative regulation of glial cell migration	1	8426.0×	4e-04	IDH2
negative regulation of matrix metallopeptidase secretion	1	8426.0×	4e-04	IDH2
isocitrate metabolic process	1	3370.4×	7e-04	IDH2
NADP+ biosynthetic process	1	2407.4×	8e-04	IDH2
negative regulation of glial cell proliferation	1	1685.2×	9e-04	IDH2
NADP+ metabolic process	1	1532.0×	9e-04	IDH2
2-oxoglutarate metabolic process	1	936.2×	0.001	IDH2
tricarboxylic acid cycle	1	510.7×	0.002	IDH2
carbohydrate metabolic process	1	135.9×	0.007	IDH2

Therapeutics

Drugs indicated for this disease

3 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Belinostat	Approved (phase 4)
Pralatrexate	Approved (phase 4)
Romidepsin	Approved (phase 4)
Azacitidine	Phase 3 (in late-stage trials)
Decitabine	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Tucidinostat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Brentuximab Vedotin, Lenalidomide, Mogamulizumab, Pembrolizumab, Selinexor.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
IDH2	ENASIDENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IDH2	7	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ENASIDENIB	4	IDH2
ENASIDENIB MESYLATE	4	IDH2
IVOSIDENIB	4	IDH2
VORASIDENIB	4	IDH2
OLUTASIDENIB	4	IDH2
CRELOSIDENIB	2	IDH2
RANOSIDENIB	2	IDH2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
IDH2	84	Binding:84

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
IDH2	1.1.1.42	isocitrate dehydrogenase (NADP+)

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

7 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
ENASIDENIB	4	IDH2
ENASIDENIB MESYLATE	4	IDH2
IVOSIDENIB	4	IDH2
VORASIDENIB	4	IDH2
OLUTASIDENIB	4	IDH2
CRELOSIDENIB	2	IDH2
RANOSIDENIB	2	IDH2

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	IDH2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 290.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	107
PHASE1	69
PHASE1/PHASE2	44
Not specified	39
PHASE3	15
EARLY_PHASE1	9
PHASE4	4
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01664975	PHASE4	COMPLETED	Treatment of Peripheral T-cell Lymphoma
NCT03071822	PHASE4	UNKNOWN	Combination Chemotherapy Including Cisplatin, Ifosfamide, Gemcitabine, L-asparaginase, Etoposide and Dexamethasone as Treatment of Newly Diagnosed and Relapsed/Refractory Peripheral T Cell Lymphomas
NCT03150602	PHASE4	UNKNOWN	A Pralatrexate Study in Asian Patients With Peripheral T-cell Lymphoma After Prior Therapy
NCT04040491	PHASE4	UNKNOWN	PD-1 Antibody, Chidamide, Lenalidomide and Gemcitabine for Peripheral T-cell Lymphoma
NCT04668690	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Study of Mitoxantrone Hydrochloride Liposome Injection vs. Chidamide in Patients With Relapsed/Refractory PTCL
NCT06072131	PHASE3	RECRUITING	To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
NCT06548347	PHASE2/PHASE3	NOT_YET_RECRUITING	A Phase II/III Study of Linperlisib Plus CHOP Versus CHOP in Patients With Newly Diagnosed Peripheral T Cell Lymphoma
NCT07234162	PHASE3	RECRUITING	A Phase 3 Multinational Study of Golidocitinib Versus Investigator’s Choice in r/r PTCL (JACKPOT19)
NCT07258680	PHASE3	ENROLLING_BY_INVITATION	BrEto-TCL - Defining the Role of Brentuximab and Etoposide for Optimizing First-line Therapy of T-cell Lymphomas
NCT07389616	PHASE2/PHASE3	RECRUITING	A Clinical Trial of Cidabenamine Plus Azacitidine to Prevent Post-Transplant Progression in High-Risk Peripheral T-Cell Lymphoma
NCT07414758	PHASE3	RECRUITING	Golidocitinib Versus Placebo as Maintenance Therapy in PTCL Patients With Response (CR/PR) After First-Line Chemotherapy
NCT00970385	PHASE3	COMPLETED	Study About Treatment of Newly Diagnosed Non Cutaneous Peripheral T Cell Lymphoma
NCT01355783	PHASE3	WITHDRAWN	A Phase 3 Trial of E7777 in Combination With CHOP Compared With CHOP Alone for the First-Line Treatment of Peripheral T-cell Lymphoma
NCT01420679	PHASE3	TERMINATED	Pralatrexate vs Observation Following CHOP-based Chemotherapy in Undiagnosed Peripheral T-cell Lymphoma Patients
NCT01482962	PHASE3	COMPLETED	Alisertib (MLN8237) or Investigator’s Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
NCT01796002	PHASE3	COMPLETED	Efficacy and Safety of Romidepsin CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma
NCT03023358	PHASE3	UNKNOWN	Compared the Efficacy and Safety of CDOP Combined With Chidamide and CDOP in de Novo Peripheral T Cell Lymphoma Patients
NCT03349333	PHASE3	COMPLETED	A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL
NCT03553537	PHASE3	UNKNOWN	Efficacy and Safety of Decitabine Plus CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma
NCT03952572	PHASE3	UNKNOWN	Efficacy and Safety of CDOP vs CHOP for Newly Diagnosed Peripheral T-cell Lymphoma
NCT04021082	PHASE2/PHASE3	WITHDRAWN	CELTIC-1: A Phase 2B Study of Cerdulatinib in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
NCT04880746	PHASE3	UNKNOWN	Efficacy and Safety of Cladribine Combined With BEAC Pretreatment Regimen in the Treatment of Peripheral T-cell Lymphoma: a Multicenter Clinical Study
NCT02797470	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant
NCT02978625	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
NCT03113500	PHASE2	ACTIVE_NOT_RECRUITING	Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
NCT03278782	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Pembrolizumab (MK-3475) in Combination With Romidepsin
NCT03598998	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Pembrolizumab and Pralatrexate in Treating Patients With Relapsed or Refractory Peripheral T-Cell Lymphomas
NCT03922724	PHASE2	RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
NCT04068597	PHASE1/PHASE2	RECRUITING	Study to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies
NCT04083495	PHASE2	RECRUITING	CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma
NCT04390737	PHASE1/PHASE2	RECRUITING	Evaluate the Safety and Clinical Activity of HH2853
NCT04512534	PHASE2	RECRUITING	Sintilimab Combined With Chidamide in Treating Peripheral T Cell Lymphoma
NCT04747236	PHASE2	RECRUITING	Randomized Phase IIB Trial of Oral Azacytidine Plus Romidepsin Versus Investigator’s Choice in PTCL
NCT04922567	PHASE2	RECRUITING	Efficacy and Safety of Lenalidomide Plus CHOP vs CHOP in Patients With Untreated Peripheral T-Cell Lymphoma
NCT04984837	PHASE2	RECRUITING	Study of Lacutamab in Peripheral T-cell Lymphoma
NCT05675813	PHASE1/PHASE2	RECRUITING	Genotype-guided Treatment in Newly Diagnosed PTCL
NCT05749549	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Phase I/IIa Study of BR1733 in Subjects With Advanced Cancers
NCT05949944	PHASE1/PHASE2	RECRUITING	Linperlisib in Combination With CHOP in Previously Untreated Peripheral T-Cell Lymphoma
NCT05958719	PHASE2	RECRUITING	Chidamide in Combination With Azacitidine, Liposomal Mitoxantrone, and Prednisone (CAMP Regimen) for the Treatment of Previously Untreated Nodal TFH Cell Lymphoma
NCT05963347	PHASE2	RECRUITING	Go-CHOP as the Frontline Therapy for PTCL

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROMIDEPSIN	4	19
PRALATREXATE	4	15
BELINOSTAT	4	7
DENILEUKIN DIFTITOX	4	5
ALEMTUZUMAB	4	4
CYANOCOBALAMIN	4	4
DUVELISIB	4	4
BENDAMUSTINE HYDROCHLORIDE	4	3
BRENTUXIMAB VEDOTIN	4	3
MOGAMULIZUMAB	4	3
RUXOLITINIB	4	3
TISLELIZUMAB	4	3
BORTEZOMIB D-MANNITOL	4	2
GEMCITABINE	4	2
IFOSFAMIDE	4	2
PANOBINOSTAT	4	2
PENTOSTATIN	4	2
SELINEXOR	4	2
TAZEMETOSTAT	4	2
ASPARAGINASE	4	1
AZACITIDINE	4	1
BLEOMYCIN	4	1
CALASPARGASE PEGOL	4	1
CISPLATIN	4	1
CLOFARABINE	4	1
DECITABINE	4	1
DEFERASIROX	4	1
DEXRAZOXANE	4	1
DEXRAZOXANE HYDROCHLORIDE	4	1
ELRANATAMAB	4	1