angioimmunoblastic T-cell lymphoma

Summary

angioimmunoblastic T-cell lymphoma (MONDO:0004977) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 3 ClinVar predisposition records) and 122 clinical trials. Top therapeutic interventions include bendamustine, romidepsin, and alemtuzumab.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (United States) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 3
• Clinical trials: 122

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000	0.05	United States	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	angioimmunoblastic T-cell lymphoma
Mondo ID	MONDO:0004977
EFO	EFO:0000255
MeSH	D007119
Orphanet	86886
DOID	DOID:0111147
ICD-10-CM	C86.5
ICD-11	1254954229
NCIT	C7528
SNOMED CT	413537009
UMLS	C0020981
MedGen	7025
GARD	0011973
MedDRA	10002449
NORD	784
Is cancer (heuristic)	yes

Also known as: AILD · AILT · AITL · angioimmunoblastic lymphadenopathy · angioimmunoblastic lymphadenopathy type T-cell lymphoma · angioimmunoblastic lymphadenopathy with Dysproteinemia · angioimmunoblastic T-cell lymphoma · immunoblastic lymphadenopathy · lymphogranulomatosis X · T-cell lymphoma, AILD type

Data availability: 3 ClinVar variants.

Disease family

Classification path: 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 › angioimmunoblastic T-cell lymphoma

Related subtypes (7): 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

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2033736	NM_001127208.3(TET2):c.3765C>A (p.Tyr1255Ter)	TET2	Pathogenic	criteria provided, single submitter
2664682	NM_001127208.3(TET2):c.3893del (p.Cys1298fs)	TET2	Pathogenic	criteria provided, single submitter
430399	NM_001127208.3(TET2):c.4145A>G (p.His1382Arg)	TET2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TET2	LoF	AML,MDS,MLYM,NHL,PCM,RCC,SOFT_TISSUE	CIViC #55

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TET2	Orphanet:100019	Myelodysplastic neoplasm with increased blasts type 1
TET2	Orphanet:100020	Myelodysplastic neoplasm with increased blasts type 2
TET2	Orphanet:3318	Essential thrombocythemia
TET2	Orphanet:664729	EBV-induced lymphoproliferative disease due to TET2 deficiency
TET2	Orphanet:75564	Acquired idiopathic sideroblastic anemia
TET2	Orphanet:824	Primary myelofibrosis
TET2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
TET2	Orphanet:98826	Myelodysplastic neoplasm with low blasts
TET2	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
TET2	Orphanet:98850	Aggressive systemic mastocytosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TET2	HGNC:25941	ENSG00000168769	Q6N021	Methylcytosine dioxygenase TET2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TET2	Other/Unknown	no		2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase

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
amniotic fluid	1
epithelium of nasopharynx	1
palpebral conjunctiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TET2	249	ubiquitous	marker	palpebral conjunctiva, amniotic fluid, epithelium of nasopharynx

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TET2	2,965

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TET2	Q6N021	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
TET1,2,3 and TDG demethylate DNA	1	2855.0×	0.002	TET2
Specification of primordial germ cells	1	878.5×	0.003	TET2
Reproduction	1	190.3×	0.009	TET2
Epigenetic regulation of gene expression	1	71.4×	0.018	TET2
Gene expression (Transcription)	1	17.8×	0.056	TET2

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
leukocyte differentiation	1	3370.4×	0.001	TET2
positive regulation of gene expression via chromosomal CpG island demethylation	1	1203.7×	0.002	TET2
myeloid cell differentiation	1	648.1×	0.003	TET2
protein O-linked glycosylation	1	224.7×	0.006	TET2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	TET2

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Alemtuzumab	Phase 3 (in late-stage trials)
Azacitidine	Phase 3 (in late-stage trials)
Bendamustine	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Romidepsin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cisplatin, Fludarabine Phosphate, Melphalan, Methotrexate, Methylprednisolone, Mycophenolate Mofetil, Prednisolone, Prednisone, Rituximab, Sintilimab, Tacrolimus Anhydrous, Tucidinostat, Vincristine.

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
TET2	VADADUSTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TET2	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
VADADUSTAT	4	TET2
PANOBINOSTAT	4	TET2
DEFEROXAMINE	4	TET2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TET2	24	Binding:24

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

2 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)
VADADUSTAT	4	TET2
DEFEROXAMINE	4	TET2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TET2
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: 122.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	41
PHASE2	37
PHASE1/PHASE2	20
Not specified	15
PHASE3	3
EARLY_PHASE1	3
PHASE4	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07046182	PHASE4	ACTIVE_NOT_RECRUITING	Clinical Study of CEP+Dasatinib + Azacytidine in First-line Treatment of. Angioimmunoblastoma Foresight
NCT01746992	PHASE4	UNKNOWN	CTOP/ITE/MTX Compared With CHOP as the First-line Therapy for Newly Diagnosed Young Patients With T Cell Lymphoma
NCT06561048	PHASE3	RECRUITING	Soquelitinib vs Standard of Care in Participants With Relapsed/Refractory Peripheral T-cell Lymphoma Not Otherwise Specified, Follicular Helper T-cell Lymphomas, or Systemic Anaplastic Large-cell Lymphoma
NCT00725231	PHASE3	UNKNOWN	Immunotherapy in Peripheral T Cell Lymphoma - the Role of Alemtuzumab in Addition to Dose Dense CHOP
NCT03593018	PHASE3	COMPLETED	Efficacy and Safety of Oral Azacitidine Compared to Investigator’s Choice Therapy in Patients With Relapsed or Refractory AITL
NCT04021082	PHASE2/PHASE3	WITHDRAWN	CELTIC-1: A Phase 2B Study of Cerdulatinib in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
NCT02223208	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Ro Plus CHOEP as First Line Treatment Before HSCT in Young Patients With Nodal Peripheral T-cell Lymphomas
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
NCT06137144	PHASE1/PHASE2	RECRUITING	AZD3470 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Haematologic Malignancies.
NCT07058103	PHASE2	RECRUITING	Tislelizumab , Cyclophosphamide, Mitoxantrone Liposomes, Chidamide, and Prednisone in the Treatment of R/R AITL
NCT00005080	PHASE2	COMPLETED	506U78 in Treating Patients With Lymphoma
NCT00005950	PHASE2	TERMINATED	506U78 in Treating Patients With Recurrent or Refractory Non-Hodgkin’s Lymphoma or T-cell Lymphoma
NCT00006251	PHASE1/PHASE2	COMPLETED	Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Donor Stem Cell Transplant Followed by Cyclosporine, Mycophenolate Mofetil, Donor Lymphocyte Infusion in Treating Patients With Hematopoietic Cancer
NCT00006473	PHASE2	COMPLETED	Oxaliplatin in Treating Patients With Relapsed or Refractory Non-Hodgkin’s Lymphoma
NCT00040846	PHASE2	COMPLETED	Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological Malignancies
NCT00049504	PHASE2	COMPLETED	Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer
NCT00072514	PHASE2	COMPLETED	Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies
NCT00078858	PHASE1/PHASE2	COMPLETED	Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant
NCT00089011	PHASE2	COMPLETED	Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer
NCT00112723	PHASE1/PHASE2	TERMINATED	Flavopiridol in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
NCT00118352	PHASE2	COMPLETED	Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
NCT00131937	PHASE2	COMPLETED	Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin’s Lymphoma
NCT00601718	PHASE1/PHASE2	COMPLETED	Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma
NCT00644189	PHASE1/PHASE2	COMPLETED	Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma
NCT00901147	PHASE2	COMPLETED	Study of Bortezomib and Panobinostat in Treating Patients With Relapsed/Refractory Peripheral T-cell Lymphoma or NK/T-cell Lymphoma
NCT00918333	PHASE1/PHASE2	COMPLETED	Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
NCT01075321	PHASE1/PHASE2	COMPLETED	Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma
NCT01110135	PHASE2	COMPLETED	Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma
NCT01177371	PHASE2	COMPLETED	High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma
NCT01198665	PHASE1/PHASE2	COMPLETED	RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
NCT01258998	PHASE2	COMPLETED	Study of Akt Inhibitor MK2206 in Patients With Relapsed Lymphoma
NCT01261247	PHASE2	COMPLETED	Panobinostat in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma
NCT01273766	PHASE2	COMPLETED	Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies
NCT01326702	PHASE1/PHASE2	COMPLETED	Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors
NCT01336933	PHASE2	COMPLETED	Combination Chemotherapy and Pralatrexate as First-Line Therapy in Treating Patients With Non-Hodgkin Lymphoma
NCT01419795	PHASE2	TERMINATED	Lenalidomide With or Without Rituximab in Treating Patients With Progressive or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, or Non-Hodgkin Lymphoma Previously Treated With Donor Stem Cell Transplant
NCT01427881	PHASE2	COMPLETED	Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
NCT01466881	PHASE2	COMPLETED	Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BENDAMUSTINE	4	4
ROMIDEPSIN	4	4
ALEMTUZUMAB	4	3
BELINOSTAT	4	3
BRENTUXIMAB VEDOTIN	4	3
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
DEXRAZOXANE	4	3
DOXORUBICIN	4	3
IFOSFAMIDE	4	3
PANOBINOSTAT	4	3
PRALATREXATE	4	3
AZACITIDINE	4	2
DASATINIB ANHYDROUS	4	2
NELARABINE	4	2
CAPECITABINE	4	1
CLOFARABINE	4	1
DEFERASIROX	4	1
DUVELISIB	4	1
ENASIDENIB	4	1
ETOPOSIDE	4	1
ETOPOSIDE PHOSPHATE	4	1
FOSCARNET	4	1
FOSCARNET SODIUM	4	1
GANCICLOVIR	4	1
ISOTRETINOIN	4	1
METHOTREXATE	4	1
PREDNISONE	4	1
SORAFENIB TOSYLATE	4	1
TAZEMETOSTAT	4	1
TISLELIZUMAB	4	1