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Atlas / Disease / diffuse large B-cell lymphoma activated B-cell type

diffuse large B-cell lymphoma activated B-cell type

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Summary

diffuse large B-cell lymphoma activated B-cell type (MONDO:0850418) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 6 clinical trials. Molecularly, PIM1 L2V is associated with resistance to Ibrutinib in Diffuse Large B-cell Lymphoma Activated B-cell Type (CIViC Level D); 2 further subtype–drug associations are mapped below. Top therapeutic interventions include cyclophosphamide anhydrous, azacitidine, and carmustine.

At a glance

  • Classification: Cancer
  • Cohort genes: 1
  • Clinical trials: 6
  • Precision-medicine evidence (CIViC): 3 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical namediffuse large B-cell lymphoma activated B-cell type
Mondo IDMONDO:0850418
DOIDDOID:0080996
NCITC36081
UMLSC1333296
MedGen272545
GARD0026614
Is cancer (heuristic)yes

Data availability: 35 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › leukocyte disorder › B-cell neoplasm › neoplasm of mature B-cells › diffuse large B-cell lymphoma › diffuse large B-cell lymphoma activated B-cell type

Related subtypes (29): relapsed/refractory diffuse large B-cell lymphoma, breast diffuse large B-cell lymphoma, colorectal diffuse large B-cell lymphoma, gastric diffuse large B-cell lymphoma, liver diffuse large B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma, Leg type, primary pulmonary diffuse large B-cell lymphoma, small intestinal diffuse large B-cell lymphoma, splenic diffuse large B-cell lymphoma, thyroid gland diffuse large B-cell lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, plasmablastic lymphoma, diffuse large B-cell lymphoma of the central nervous system, T-cell/histiocyte rich large B cell lymphoma, diffuse large B-cell lymphoma with chronic inflammation, ALK-positive large B-cell lymphoma, primary effusion lymphoma, lymphomatoid granulomatosis, primary mediastinal large B-cell lymphoma, intravascular large B-cell lymphoma, high grade B-cell lymphoma, diffuse large B-cell lymphoma germinal center B-cell type, BN2 diffuse large B-cell lymphoma, EZB diffuse large B-cell lymphoma, MCD diffuse large B-cell lymphoma, N1 diffuse large B-cell lymphoma, ST2 diffuse large B-cell lymphoma, A53 diffuse large B-cell lymphoma, primary vitreoretinal large b-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: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

GeneintOGen roleCancer typesCIViC
PIM1ActDLBCLNOS,NHL,PCMCIViC #4286

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
civic_only1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
PIM1HGNC:8986ENSG00000137193P11309Serine/threonine-protein kinase pim-1civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
PIM1Serine/threonine-protein kinase pim-1Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis.

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.

FamilyGenesFoldFDR
Kinase127.7×0.036

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
PIM1Kinaseyes2.7.11.1Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
esophagus mucosa1
left uterine tube1
lower esophagus mucosa1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
PIM1263ubiquitousmarkerlower esophagus mucosa, left uterine tube, esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
PIM11,602

Structural data

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

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PIM1P11309191

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.

PathwayCohort genesFoldFDRSample cohort genes
Regulation of GBP-mediated host defense12855.0×0.001PIM1
STAT5 activation downstream of FLT3 ITD mutants11142.0×0.002PIM1
Signaling by FLT3 fusion proteins1571.0×0.002PIM1
Interleukin-4 and Interleukin-13 signaling1102.9×0.010PIM1

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 termCohort genesFoldFDRSample cohort genes
regulation of transmembrane transporter activity116852.0×6e-04PIM1
positive regulation of cardioblast proliferation116852.0×6e-04PIM1
positive regulation of cyclin-dependent protein serine/threonine kinase activity15617.3×9e-04PIM1
regulation of hematopoietic stem cell proliferation15617.3×9e-04PIM1
vitamin D receptor signaling pathway12808.7×0.001PIM1
positive regulation of protein serine/threonine kinase activity11296.3×0.003PIM1
cellular detoxification11123.5×0.003PIM1
positive regulation of brown fat cell differentiation1991.3×0.003PIM1
obsolete negative regulation of DNA-binding transcription factor activity1732.7×0.003PIM1
positive regulation of cardiac muscle cell proliferation1624.1×0.003PIM1
negative regulation of innate immune response1510.7×0.004PIM1
positive regulation of TORC1 signaling1295.6×0.006PIM1
regulation of mitotic cell cycle1240.7×0.006PIM1
cellular response to type II interferon1208.1×0.007PIM1
protein autophosphorylation1145.3×0.009PIM1
protein phosphorylation168.0×0.018PIM1
protein stabilization166.9×0.018PIM1
negative regulation of apoptotic process134.8×0.032PIM1
apoptotic process128.7×0.036PIM1
positive regulation of DNA-templated transcription127.9×0.036PIM1

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.

SymbolExample approved molecule
PIM1COLCHICINE

Top cohort targets by molecule count

SymbolMoleculesMax phase
PIM1294

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
COLCHICINE4PIM1
RUCAPARIB4PIM1
MITOXANTRONE HYDROCHLORIDE4PIM1
ABEMACICLIB4PIM1
THIORIDAZINE4PIM1
MIDOSTAURIN4PIM1
GEFITINIB4PIM1
LEFLUNOMIDE4PIM1
RESVERATROL3PIM1
MASITINIB3PIM1
ENZASTAURIN3PIM1
ALVOCIDIB3PIM1
QUERCETIN3PIM1
LESTAURTINIB3PIM1
RUBOXISTAURIN3PIM1
SILMITASERTIB2PIM1
LAUROGUADINE2PIM1
SCH-9007762PIM1
LY-20903142PIM1
NUVISERTIB2PIM1
CROZBACICLIB2PIM1
DAPOLSERTIB2PIM1
MONZOSERTIB2PIM1
SOTRASTAURIN2PIM1
GSK-4613641PIM1
SGI-17761PIM1
GSK-10596151PIM1
LGH-4471PIM1
GSK-6906931PIM1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

SymbolAssaysType breakdown
PIM11,008Binding:971, Functional:30, ADMET:4, Toxicity:3

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
PIM12.7.11.1non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

SymbolChEMBL assays
PIM11,008

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

29 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.

CompoundMax phaseCohort target (bioactivity)
COLCHICINE4PIM1
RUCAPARIB4PIM1
MITOXANTRONE HYDROCHLORIDE4PIM1
ABEMACICLIB4PIM1
THIORIDAZINE4PIM1
MIDOSTAURIN4PIM1
GEFITINIB4PIM1
LEFLUNOMIDE4PIM1
RESVERATROL3PIM1
MASITINIB3PIM1
ENZASTAURIN3PIM1
ALVOCIDIB3PIM1
QUERCETIN3PIM1
LESTAURTINIB3PIM1
RUBOXISTAURIN3PIM1
SILMITASERTIB2PIM1
LAUROGUADINE2PIM1
SCH-9007762PIM1
LY-20903142PIM1
NUVISERTIB2PIM1
CROZBACICLIB2PIM1
DAPOLSERTIB2PIM1
MONZOSERTIB2PIM1
SOTRASTAURIN2PIM1
GSK-4613641PIM1
SGI-17761PIM1
GSK-10596151PIM1
LGH-4471PIM1
GSK-6906931PIM1

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1PIM1
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug0

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: 6.

Phase distribution (across all retrieved trials)

PhaseTrials
PHASE22
PHASE12
PHASE31
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02443077PHASE3ACTIVE_NOT_RECRUITINGIbrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma
NCT04799275PHASE2/PHASE3ACTIVE_NOT_RECRUITINGTesting CC-486 (Oral Azacitidine) Plus the Standard Drug Therapy in Patients 75 Years or Older With Newly Diagnosed Diffuse Large B Cell Lymphoma
NCT03038672PHASE2ACTIVE_NOT_RECRUITINGNivolumab With or Without Varlilumab in Treating Patients With Relapsed or Refractory Aggressive B-cell Lymphomas
NCT06834373PHASE2RECRUITINGGolcadomide and Rituximab as Bridging Therapy for Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma Before CAR T-cell Therapy
NCT05755087PHASE1RECRUITINGTegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma
NCT03742258PHASE1COMPLETEDCombination Chemotherapy and TAK-659 as Front-Line Treatment in Treating Patients With High-Risk Diffuse Large B Cell Lymphoma

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
CYCLOPHOSPHAMIDE ANHYDROUS43
AZACITIDINE41
CARMUSTINE41
IBRUTINIB41
MELPHALAN41
GOLCADOMIDE31
TEGAVIVINT21
VARLILUMAB21
CHEMBL364796401
CHEMBL446620501
CHEMBL608312901

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 3 predictive associations from 3 curated evidence items.

Molecular subtypeTherapyEffectLevelCIViC
PIM1 L2VIbrutinibResistanceCIViC DEID9945
PIM1 P81SIbrutinibResistanceCIViC DEID9946
PIM1 S97NIbrutinibResistanceCIViC DEID9947

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
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Sources 72

This page pulls from 72 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterprointogenmedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot