adult T-cell leukemia/lymphoma

Summary

adult T-cell leukemia/lymphoma (MONDO:0019471) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 103 clinical trials. Molecularly, NOTCH1 L1678P confers sensitivity to Nirogacestat in Adult T-cell Leukemia/lymphoma (CIViC Level C). Top therapeutic interventions include fludarabine phosphate, brentuximab vedotin, and foscarnet.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• Clinical trials: 103
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	adult T-cell leukemia/lymphoma
Mondo ID	MONDO:0019471
Orphanet	86875
DOID	DOID:0050523
ICD-11	430573082
NCIT	C3184
SNOMED CT	110007008
UMLS	C0023493
MedGen	44128
GARD	0019076
MedDRA	10001413
Is cancer (heuristic)	yes

Also known as: adult T-cell leukaemia · adult T-cell leukemia · adult T-cell leukemia/lymphoma · adult T-cell leukemia/lymphoma (HTLV-1 positive) · adult T-cell lymphoma · ATLL · T-cell leukaemia of adults · T-cell leukemia of adults

Data availability: 67 cell lines.

Disease family

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 › lymphoma › adult lymphoma › adult T-cell leukemia/lymphoma

Related subtypes (1): adult nodular lymphocyte predominant Hodgkin 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: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
PRKCB	Act	DLBCLNOS,HNSC,PRAD,STAD	CIViC #4517

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
PRKCB	HGNC:9395	ENSG00000166501	P05771	Protein kinase C beta type	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKCB	Protein kinase C beta type	Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, and…

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKCB	Kinase	yes	2.7.11.13	C2_dom, Prot_kinase_dom, AGC-kinase_C

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
frontal pole	1
middle temporal gyrus	1
orbitofrontal cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKCB	258	broad	marker	middle temporal gyrus, orbitofrontal cortex, frontal pole

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKCB	309

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKCB	P05771	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 42. 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
Disinhibition of SNARE formation	1	2284.0×	0.008	PRKCB
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	1427.5×	0.008	PRKCB
Downstream signaling events of B Cell Receptor (BCR)	1	815.7×	0.008	PRKCB
Glutamate binding, activation of AMPA receptors and synaptic plasticity	1	761.3×	0.008	PRKCB
Depolymerization of the Nuclear Lamina	1	761.3×	0.008	PRKCB
WNT5A-dependent internalization of FZD4	1	761.3×	0.008	PRKCB
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.008	PRKCB
VEGFR2 mediated cell proliferation	1	571.0×	0.008	PRKCB
Trafficking of AMPA receptors	1	543.8×	0.008	PRKCB
Nuclear Envelope Breakdown	1	456.8×	0.008	PRKCB
RHO GTPases Activate NADPH Oxidases	1	456.8×	0.008	PRKCB
Mitotic Prophase	1	368.4×	0.009	PRKCB
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	PRKCB
PCP/CE pathway	1	300.5×	0.010	PRKCB
Beta-catenin independent WNT signaling	1	292.8×	0.010	PRKCB
G alpha (z) signalling events	1	233.1×	0.011	PRKCB
Signaling by VEGF	1	219.6×	0.011	PRKCB
Activation of NF-kappaB in B cells	1	196.9×	0.012	PRKCB
Response to elevated platelet cytosolic Ca2+	1	163.1×	0.014	PRKCB
Transcriptional regulation by RUNX1	1	146.4×	0.014	PRKCB
VEGFA-VEGFR2 Pathway	1	139.3×	0.014	PRKCB
Signaling by WNT	1	112.0×	0.017	PRKCB
Platelet activation, signaling and aggregation	1	105.7×	0.017	PRKCB
Neurotransmitter receptors and postsynaptic signal transmission	1	100.2×	0.017	PRKCB
Transmission across Chemical Synapses	1	76.1×	0.022	PRKCB
RHO GTPase Effectors	1	68.0×	0.024	PRKCB
M Phase	1	66.0×	0.024	PRKCB
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.029	PRKCB
Cell Cycle, Mitotic	1	48.2×	0.030	PRKCB
Neuronal System	1	44.3×	0.031	PRKCB

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
cellular response to carbohydrate stimulus	1	8426.0×	0.002	PRKCB
protein kinase C signaling	1	4213.0×	0.002	PRKCB
negative regulation of D-glucose transmembrane transport	1	3370.4×	0.002	PRKCB
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	2106.5×	0.002	PRKCB
regulation of D-glucose transmembrane transport	1	2106.5×	0.002	PRKCB
mitotic nuclear membrane disassembly	1	1872.4×	0.002	PRKCB
positive regulation of ferroptosis	1	1532.0×	0.002	PRKCB
positive regulation of vascular endothelial growth factor receptor signaling pathway	1	1053.2×	0.003	PRKCB
lipoprotein transport	1	991.3×	0.003	PRKCB
B cell activation	1	455.5×	0.005	PRKCB
presynaptic modulation of chemical synaptic transmission	1	455.5×	0.005	PRKCB
regulation of synaptic vesicle exocytosis	1	455.5×	0.005	PRKCB
B cell receptor signaling pathway	1	401.2×	0.005	PRKCB
negative regulation of insulin receptor signaling pathway	1	374.5×	0.005	PRKCB
positive regulation of insulin secretion	1	255.3×	0.007	PRKCB
calcium ion transport	1	181.2×	0.009	PRKCB
intracellular calcium ion homeostasis	1	145.3×	0.010	PRKCB
positive regulation of angiogenesis	1	115.4×	0.012	PRKCB
adaptive immune response	1	84.3×	0.016	PRKCB
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.017	PRKCB
protein phosphorylation	1	68.0×	0.018	PRKCB
intracellular signal transduction	1	38.1×	0.030	PRKCB
apoptotic process	1	28.7×	0.038	PRKCB
signal transduction	1	16.1×	0.065	PRKCB
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PRKCB

Therapeutics

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
PRKCB	INGENOL MEBUTATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKCB	28	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INGENOL MEBUTATE	4	PRKCB
MIDOSTAURIN	4	PRKCB
TAMOXIFEN	4	PRKCB
PACRITINIB	4	PRKCB
BARICITINIB	4	PRKCB
CAPIVASERTIB	4	PRKCB
ABEMACICLIB	4	PRKCB
SURAMIN	3	PRKCB
FASUDIL	3	PRKCB
ALVOCIDIB	3	PRKCB
ENZASTAURIN HYDROCHLORIDE	3	PRKCB
AFURESERTIB	3	PRKCB
ENZASTAURIN	3	PRKCB
RUBOXISTAURIN	3	PRKCB
PHORBOL MYRISTATE ACETATE	2	PRKCB
EDELFOSINE	2	PRKCB
UPROSERTIB	2	PRKCB
UCN-01	2	PRKCB
DORAMAPIMOD	2	PRKCB
ZOTIRACICLIB	2	PRKCB
DECERNOTINIB	2	PRKCB
LY-2090314	2	PRKCB
DAROVASERTIB	2	PRKCB
AT-9283	2	PRKCB
SOTRASTAURIN	2	PRKCB
PF-03758309	1	PRKCB
GSK-690693	1	PRKCB
Y-39983	1	PRKCB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PRKCB	973	Binding:951, Functional:21, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRKCB	2.7.11.13	protein kinase C

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PRKCB	973

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

27 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)
INGENOL MEBUTATE	4	PRKCB
MIDOSTAURIN	4	PRKCB
TAMOXIFEN	4	PRKCB
PACRITINIB	4	PRKCB
BARICITINIB	4	PRKCB
CAPIVASERTIB	4	PRKCB
ABEMACICLIB	4	PRKCB
SURAMIN	3	PRKCB
FASUDIL	3	PRKCB
ENZASTAURIN HYDROCHLORIDE	3	PRKCB
AFURESERTIB	3	PRKCB
ENZASTAURIN	3	PRKCB
RUBOXISTAURIN	3	PRKCB
PHORBOL MYRISTATE ACETATE	2	PRKCB
EDELFOSINE	2	PRKCB
UPROSERTIB	2	PRKCB
UCN-01	2	PRKCB
DORAMAPIMOD	2	PRKCB
ZOTIRACICLIB	2	PRKCB
DECERNOTINIB	2	PRKCB
LY-2090314	2	PRKCB
DAROVASERTIB	2	PRKCB
AT-9283	2	PRKCB
SOTRASTAURIN	2	PRKCB
PF-03758309	1	PRKCB
GSK-690693	1	PRKCB
Y-39983	1	PRKCB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRKCB
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: 103.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1	42
PHASE2	37
Not specified	11
PHASE1/PHASE2	9
EARLY_PHASE1	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00145002	PHASE3	COMPLETED	A Study for Aggressive Adult T-cell Leukemia-lymphoma (ATLL)
NCT03113500	PHASE2	ACTIVE_NOT_RECRUITING	Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
NCT03264131	PHASE2	ACTIVE_NOT_RECRUITING	BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma
NCT04703192	PHASE2	ACTIVE_NOT_RECRUITING	Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
NCT05031897	PHASE2	RECRUITING	Two Step Haplo With Radiation Conditioning
NCT07075328	PHASE1/PHASE2	RECRUITING	A Phase I/II Study of OJP-001 in Patients With Adult T-cell Leukemia/Lymphoma
NCT07159620	PHASE2	RECRUITING	Venetoclax Combined With Azacitidine, Chidamide, Vindesine, and Dexamethasone in Newly Diagnosed ETP-ALL Like Patients
NCT07356245	PHASE2	RECRUITING	Ruxolitinib Maintenance Post-Hematopoietic Stem Cell Transplant T-Cell Lymphoma
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
NCT00082888	PHASE2	COMPLETED	Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma
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
NCT00489203	PHASE2	COMPLETED	Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
NCT00918333	PHASE1/PHASE2	COMPLETED	Panobinostat and Everolimus in Treating Patients With Recurrent Multiple Myeloma, Non-Hodgkin Lymphoma, or Hodgkin Lymphoma
NCT00924170	PHASE1/PHASE2	COMPLETED	Phase II Trial of LMB-2, Fludarabine and Cyclophosphamide for Adult T-Cell Leukemia
NCT01044745	PHASE2	TERMINATED	Rituximab in Preventing Acute Graft-Versus-Host Disease in a Donor Stem Cell Transplant for Hematologic Cancer
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
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
NCT01274533	PHASE2	COMPLETED	Lenalidomide in HTLV-1 Adult T-Cell Leukemia
NCT01326702	PHASE1/PHASE2	COMPLETED	Veliparib, Bendamustine Hydrochloride, and Rituximab in Treating Patients With Relapsed or Refractory Lymphoma, Multiple Myeloma, or Solid Tumors
NCT01378871	PHASE2	TERMINATED	A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/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
NCT01529827	PHASE2	COMPLETED	Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01652014	PHASE2	WITHDRAWN	Single or Double Donor Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematologic Malignancies
NCT01805037	PHASE1/PHASE2	TERMINATED	Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	17
BRENTUXIMAB VEDOTIN	4	4
FOSCARNET	4	4
BELINOSTAT	4	3
BENDAMUSTINE HYDROCHLORIDE	4	3
ALEMTUZUMAB	4	2
MOGAMULIZUMAB	4	2
NELARABINE	4	2
PANOBINOSTAT	4	2
BECLOMETHASONE DIPROPIONATE	4	1
DEFERASIROX	4	1
DUVELISIB	4	1
ETOPOSIDE PHOSPHATE	4	1
GANCICLOVIR	4	1
ISOTRETINOIN	4	1
ROMIDEPSIN	4	1
SORAFENIB TOSYLATE	4	1
VALGANCICLOVIR	4	1
VINCRISTINE SULFATE	4	1
VINDESINE	4	1
TANESPIMYCIN	3	4
ALVOCIDIB	3	3
ALISERTIB	3	2
VELIPARIB	3	2
6-O-BENZYLGUANINE	3	1
ALBINTERFERON ALFA-2B	3	1
CEDIRANIB MALEATE	3	1
CILENGITIDE	3	1
CPI 613	3	1
ENTINOSTAT	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 1 curated evidence items; also 1 prognostic, 1 oncogenic, 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
NOTCH1 L1678P	Nirogacestat	Sensitivity/Response	CIViC C	EID5921