Myeloproliferative neoplasm, unclassifiable

Summary

Myeloproliferative neoplasm, unclassifiable (MONDO:0019452) is a cancer with 7 cohort genes (6 CIViC-evidence somatic drivers; 23 ClinVar predisposition records) and 50 clinical trials. Top therapeutic interventions include fludarabine phosphate, foscarnet, and dacomitinib anhydrous.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 7
• ClinVar variants: 23
• Clinical trials: 50

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.53	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	myeloproliferative neoplasm, unclassifiable
Mondo ID	MONDO:0019452
Orphanet	86830
NCIT	C27350
UMLS	C1333046
MedGen	232365
GARD	0016764
Is cancer (heuristic)	yes

Also known as: chronic myeloproliferative disease, unclassifiable · chronic myeloproliferative disorder, unclassifiable · CMPD, U · CMPD-U · MPN, U · MPN-U · myeloproliferative neoplasm, unclassifiable · unclassifiable chronic myeloproliferative disease · unclassifiable chronic myeloproliferative disorder · undifferentiated myeloproliferative disease

Data availability: 23 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › 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 › myeloid neoplasm › myeloproliferative neoplasm › myeloproliferative neoplasm, unclassifiable

Related subtypes (12): myeloid leukemia, essential thrombocythemia, myelodysplastic/myeloproliferative neoplasm, therapy-related myeloid neoplasm, transient myeloproliferative syndrome, primary myelofibrosis, myeloproliferative disease, autosomal recessive, thrombocytopenia 6, chronic eosinophilic leukemia, chronic neutrophilic leukemia, erythroid neoplasm, myelofibrosis

Subtypes (1): myeloproliferative disorder, chronic, with eosinophilia

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

23 retrieved; paginated sample, class counts are floors:

8 conflicting classifications of pathogenicity, 6 benign/likely benign, 4 benign, 3 uncertain significance, 1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1705890	NM_000314.8(PTEN):c.-326=	PTEN	Pathogenic	criteria provided, single submitter
1705891	NM_001304717.5(PTEN):c.140GGC[5] (p.Arg52del)	PTEN	Likely pathogenic	criteria provided, single submitter
1705889	NM_002221.4(ITPKB):c.964G>A (p.Ala322Thr)	ITPKB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705896	NM_002221.4(ITPKB):c.267CAGCGGCAG[1] (p.91GSS[1])	ITPKB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705898	NM_002221.4(ITPKB):c.518G>A (p.Arg173His)	ITPKB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404453	NM_001042492.3(NF1):c.3395G>A (p.Arg1132His)	NF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705900	NM_017617.5(NOTCH1):c.2296G>A (p.Gly766Ser)	NOTCH1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135024	NM_006206.6(PDGFRA):c.167G>C (p.Ser56Thr)	PDGFRA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1165836	NM_003200.5(TCF3):c.1475C>T (p.Ala492Val)	TCF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1670612	NM_003200.5(TCF3):c.1422C>A (p.Asp474Glu)	TCF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1705893	NM_003200.5(TCF3):c.760G>T (p.Gly254Cys)	TCF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1705894	NM_003200.5(TCF3):c.1303C>G (p.Leu435Val)	TCF3	Uncertain significance	criteria provided, single submitter
1705895	NM_003200.5(TCF3):c.632C>A (p.Pro211His)	TCF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1705892	NM_002221.4(ITPKB):c.220G>A (p.Gly74Ser)	ITPKB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1705897	NM_002221.4(ITPKB):c.1655C>A (p.Pro552Gln)	ITPKB	Benign	criteria provided, multiple submitters, no conflicts
1705899	NM_002221.4(ITPKB):c.1222T>G (p.Ser408Ala)	ITPKB	Benign	criteria provided, multiple submitters, no conflicts
133374	NM_006206.6(PDGFRA):c.2323+1120C>T	LOC126807054	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1243966	NM_017617.5(NOTCH1):c.52G>A (p.Ala18Thr)	NOTCH1	Benign	criteria provided, multiple submitters, no conflicts
134934	NM_017617.5(NOTCH1):c.4129C>T (p.Pro1377Ser)	NOTCH1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
41794	NM_006206.6(PDGFRA):c.1432T>C (p.Ser478Pro)	PDGFRA	Benign	criteria provided, multiple submitters, no conflicts
41801	NM_006206.6(PDGFRA):c.661C>T (p.Leu221Phe)	PDGFRA	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
810888	NM_000314.8(PTEN):c.-511G>A	PTEN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1167884	NM_003200.5(TCF3):c.1291G>A (p.Gly431Ser)	TCF3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 34 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TCF3			CIViC #5646
ITPKB			CIViC #3083
NF1	LoF	ACC,ALL,AML,ANGS,BLCA,BRCA,CCRCC,CHOL,CLLSLL,COADREAD,GB,GBM,GIST,HCC,HNSC,LGGNOS,LMS,LUAD,LUNG,LUSC,MEL,NBL,NSCLC,OVT,PAST,PGNG,PLMESO,RMS,SKCM,SOFT_TISSUE,STAD,THYM,UCS	CIViC #3867
NOTCH1	LoF	ALL,ANGS,BCC,BLCA,BRCA,CESC,CHOL,CLLSLL,CSCC,DLBCLNOS,ESCA,HNSC,LGGNOS,LUAD,LUSC,MBL,MEL,MGCT,NPC,NSCLC,OVT,READ,SACA,SCLC,SKIN,VULVA	CIViC #50
PDGFRA	Act	CSCC,GB,GBM,HGGNOS,LGGNOS,LUSC,PAST	CIViC #38
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TCF3	Orphanet:33110	Autosomal non-syndromic agammaglobulinemia
TCF3	Orphanet:585956	B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3)
TCF3	Orphanet:641375	B-lymphoblastic leukemia/lymphoma with t(17;19)
NF1	Orphanet:139474	17q11.2 microduplication syndrome
NF1	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
NF1	Orphanet:293199	Pleomorphic rhabdomyosarcoma
NF1	Orphanet:363700	Neurofibromatosis type 1 due to NF1 mutation or intragenic deletion
NF1	Orphanet:638	Neurofibromatosis-Noonan syndrome
NF1	Orphanet:86834	Juvenile myelomonocytic leukemia
NF1	Orphanet:97685	17q11 microdeletion syndrome
NF1	Orphanet:99756	Alveolar rhabdomyosarcoma
NF1	Orphanet:99757	Embryonal rhabdomyosarcoma
NOTCH1	Orphanet:402075	Familial bicuspid aortic valve
NOTCH1	Orphanet:974	Adams-Oliver syndrome
PDGFRA	Orphanet:168940	Chronic eosinophilic leukemia
PDGFRA	Orphanet:168947	Myeloid/lymphoid neoplasm associated with PDGFRA rearrangement
PDGFRA	Orphanet:199306	Cleft lip/palate
PDGFRA	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRA	Orphanet:44890	Gastrointestinal stromal tumor
PDGFRA	Orphanet:585877	B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality
PTEN	Orphanet:109	Bannayan-Riley-Ruvalcaba syndrome
PTEN	Orphanet:137608	Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome
PTEN	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PTEN	Orphanet:201	Cowden syndrome
PTEN	Orphanet:210548	Macrocephaly-intellectual disability-autism syndrome
PTEN	Orphanet:2969	Proteus-like syndrome
PTEN	Orphanet:494547	Squamous cell carcinoma of the hypopharynx
PTEN	Orphanet:494550	Squamous cell carcinoma of the larynx
PTEN	Orphanet:500464	Squamous cell carcinoma of the nasal cavity and paranasal sinuses
PTEN	Orphanet:500478	Squamous cell carcinoma of the oropharynx
PTEN	Orphanet:502363	Squamous cell carcinoma of the oral cavity
PTEN	Orphanet:502366	Squamous cell carcinoma of the lip
PTEN	Orphanet:65285	Lhermitte-Duclos disease
PTEN	Orphanet:79076	Juvenile polyposis of infancy

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TCF3	HGNC:11633	ENSG00000071564	P15923	Transcription factor E2-alpha	clinvar
TCF7L1	HGNC:11640	ENSG00000152284	Q9HCS4	Transcription factor 7-like 1	clinvar
ITPKB	HGNC:6179	ENSG00000143772	P27987	Inositol-trisphosphate 3-kinase B	clinvar
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	clinvar
NOTCH1	HGNC:7881	ENSG00000148400	P46531	Neurogenic locus notch homolog protein 1	clinvar
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	clinvar
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TCF3	Transcription factor E2-alpha	Transcriptional regulator involved in the initiation of neuronal differentiation and mesenchymal to epithelial transition.
TCF7L1	Transcription factor 7-like 1	Participates in the Wnt signaling pathway.
ITPKB	Inositol-trisphosphate 3-kinase B	Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
NOTCH1	Neurogenic locus notch homolog protein 1	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
PDGFRA	Platelet-derived growth factor receptor alpha	Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis.
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.

Protein-family classification

Druggable: 3 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.43

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
Phosphatase	1	12.0×	0.483
Kinase	1	4.0×	0.680
Scaffold/PPI	1	2.5×	0.682
Enzyme (other)	1	1.7×	0.685
Transcription factor	1	1.2×	0.714
Other/Unknown	2	0.5×	0.968

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TCF3	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TCF7L1	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
ITPKB	Enzyme (other)	yes	2.7.1.127	IPK, IPK_sf
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
NOTCH1	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom

Expression context

Cohort genes with no expression data: 0.

7 cohort genes 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)	7
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
calcaneal tendon	2
colonic epithelium	2
embryo	1
ganglionic eminence	1
aorta	1
popliteal artery	1
tibial artery	1
globus pallidus	1
lateral globus pallidus	1
substantia nigra pars reticulata	1
adrenal tissue	1
visceral pleura	1
decidua	1
synovial joint	1
tibia	1
endothelial cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TCF3	294	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
TCF7L1	230	ubiquitous	marker	popliteal artery, tibial artery, aorta
ITPKB	268	ubiquitous	marker	lateral globus pallidus, substantia nigra pars reticulata, globus pallidus
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
NOTCH1	272	ubiquitous	marker	ventricular zone, colonic epithelium, visceral pleura
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTEN	11,626
NOTCH1	7,411
NF1	5,540
PDGFRA	5,186
TCF7L1	1,635
ITPKB	768
TCF3	457

Intra-cohort edges

A	B	Sources
NF1	PDGFRA	string_interaction
NF1	PTEN	biogrid_interaction, string_interaction
PDGFRA	PTEN	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NOTCH1	P46531	29
NF1	P21359	26
PDGFRA	P16234	15
PTEN	P60484	12
TCF3	P15923	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITPKB	P27987	56.58
TCF7L1	Q9HCS4	52.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 88. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Imatinib-resistant PDGFR mutants	1	1631.4×	0.009	PDGFRA
Sunitinib-resistant PDGFR mutants	1	1631.4×	0.009	PDGFRA
Regorafenib-resistant PDGFR mutants	1	1631.4×	0.009	PDGFRA
Sorafenib-resistant PDGFR mutants	1	1631.4×	0.009	PDGFRA
PDGFR mutants bind TKIs	1	1631.4×	0.009	PDGFRA
Synthesis of IP3 and IP4 in the cytosol	2	120.8×	0.009	ITPKB, PTEN
PTEN Loss of Function in Cancer	1	815.7×	0.015	PTEN
Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling	1	326.3×	0.030	NOTCH1
Defective LFNG causes SCDO3	1	326.3×	0.030	NOTCH1
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	271.9×	0.031	NOTCH1
Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1	233.1×	0.031	NOTCH1
RAS signaling downstream of NF1 loss-of-function variants	1	233.1×	0.031	NF1
Regulation of NFE2L2 gene expression	1	203.9×	0.032	NOTCH1
Binding of TCF/LEF:CTNNB1 to target gene promoters	1	163.1×	0.032	TCF7L1
Regulation of PTEN mRNA translation	1	163.1×	0.032	PTEN
RUNX3 regulates WNT signaling	1	163.1×	0.032	TCF7L1
RAF/MAP kinase cascade	2	17.4×	0.032	NF1, PDGFRA
Regulation of PTEN localization	1	148.3×	0.033	PTEN
NFE2L2 regulating tumorigenic genes	1	135.9×	0.033	NOTCH1
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	1	125.5×	0.033	PDGFRA
Signaling by PDGFRA extracellular domain mutants	1	125.5×	0.033	PDGFRA
RUNX3 regulates NOTCH signaling	1	116.5×	0.034	NOTCH1
Constitutive Signaling by NOTCH1 HD Domain Mutants	1	108.8×	0.034	NOTCH1
Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells	1	102.0×	0.034	NOTCH1
Repression of WNT target genes	1	102.0×	0.034	TCF7L1
Pre-NOTCH Processing in Golgi	1	90.6×	0.036	NOTCH1
Specification of the neural plate border	1	90.6×	0.036	TCF7L1
MECP2 regulates neuronal receptors and channels	1	85.9×	0.036	NOTCH1
NOTCH4 Intracellular Domain Regulates Transcription	1	81.6×	0.036	NOTCH1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	1	81.6×	0.036	TCF7L1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
forebrain morphogenesis	2	401.2×	0.003	NF1, PTEN
negative regulation of oligodendrocyte differentiation	2	321.0×	0.003	NF1, NOTCH1
positive regulation of Ras protein signal transduction	2	253.4×	0.003	ITPKB, NOTCH1
adrenal gland development	2	192.6×	0.004	NF1, PDGFRA
neural tube development	2	150.5×	0.004	NF1, NOTCH1
heart development	3	33.8×	0.004	NF1, NOTCH1, PTEN
oligodendrocyte differentiation	2	120.4×	0.006	NF1, NOTCH1
coronary sinus valve morphogenesis	1	2407.4×	0.007	NOTCH1
Notch signaling pathway involved in regulation of secondary heart field cardioblast proliferation	1	2407.4×	0.007	NOTCH1
foregut morphogenesis	1	2407.4×	0.007	NOTCH1
positive regulation of mast cell apoptotic process	1	2407.4×	0.007	NF1
negative regulation of neutrophil apoptotic process	1	2407.4×	0.007	ITPKB
regulation of glial cell differentiation	1	2407.4×	0.007	NF1
regulation of epithelial cell proliferation involved in prostate gland development	1	2407.4×	0.007	NOTCH1
venous endothelial cell differentiation	1	2407.4×	0.007	NOTCH1
observational learning	1	2407.4×	0.007	NF1
endocardium morphogenesis	1	1203.7×	0.007	NOTCH1
coronary vein morphogenesis	1	1203.7×	0.007	NOTCH1
cardiac right atrium morphogenesis	1	1203.7×	0.007	NOTCH1
growth involved in heart morphogenesis	1	1203.7×	0.007	NOTCH1
obsolete negative regulation of cell proliferation involved in heart valve morphogenesis	1	1203.7×	0.007	NOTCH1
cell differentiation in spinal cord	1	1203.7×	0.007	NOTCH1
platelet-derived growth factor receptor-alpha signaling pathway	1	1203.7×	0.007	PDGFRA
gamma-aminobutyric acid secretion, neurotransmission	1	1203.7×	0.007	NF1
positive regulation of aorta morphogenesis	1	1203.7×	0.007	NOTCH1
negative regulation of synaptic vesicle clustering	1	1203.7×	0.007	PTEN
mitral valve formation	1	802.5×	0.007	NOTCH1
cardiac chamber formation	1	802.5×	0.007	NOTCH1
auditory receptor cell fate commitment	1	802.5×	0.007	NOTCH1
Schwann cell proliferation	1	802.5×	0.007	NF1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 5

Druggability breadth: 4 of 7 evidence-associated genes (57%) 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
PDGFRA	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRA	77	4
NOTCH1	1	2
TCF3	0	0
TCF7L1	0	0
ITPKB	0	0
NF1	0	0
PTEN	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRA
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA
SARACATINIB	3	PDGFRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
NOTCH1	23	Binding:19, ADMET:4
PTEN	8	Binding:8
ITPKB	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ITPKB	2.7.1.127	inositol-trisphosphate 3-kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PDGFRA	1,172

Pharmacogenomics

Cohort genes with a PharmGKB record: 7; 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.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	PDGFRA
TIVOZANIB	4	PDGFRA
LENVATINIB	4	PDGFRA
AXITINIB	4	PDGFRA
SORAFENIB	4	PDGFRA
IMATINIB MESYLATE	4	PDGFRA
INFIGRATINIB PHOSPHATE	4	PDGFRA
INFIGRATINIB	4	PDGFRA
REGORAFENIB	4	PDGFRA
CERITINIB	4	PDGFRA
VANDETANIB	4	PDGFRA
NILOTINIB	4	PDGFRA
BOSUTINIB	4	PDGFRA
NINTEDANIB ESYLATE	4	PDGFRA
PEXIDARTINIB	4	PDGFRA
AVAPRITINIB	4	PDGFRA
RIPRETINIB	4	PDGFRA
PAZOPANIB	4	PDGFRA
NINTEDANIB	4	PDGFRA
SUNITINIB	4	PDGFRA
DASATINIB	4	PDGFRA
ERLOTINIB	4	PDGFRA
QUIZARTINIB	4	PDGFRA
MIDOSTAURIN	4	PDGFRA
IMATINIB	4	PDGFRA
VATALANIB	3	PDGFRA
MASITINIB	3	PDGFRA
CRENOLANIB	3	PDGFRA
SARACATINIB	3	PDGFRA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDGFRA
B	Phased (≥1) drug, not yet approved	1	NOTCH1
C	Druggable family + PDB, no drug	1	PTEN
D	Druggable family + AlphaFold only, no drug	1	ITPKB
E	Difficult family or no structure, no drug	3	TCF3, TCF7L1, NF1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TCF3	0	—
TCF7L1	0	—
ITPKB	2	—
NF1	0	—
PTEN	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 50.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	17
Not specified	14
PHASE1	12
PHASE1/PHASE2	4
PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00322101	PHASE3	COMPLETED	Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia
NCT00799461	PHASE3	COMPLETED	Internet-Based Program With or Without Telephone-Based Problem-Solving Training in Helping Long-Term Survivors of Hematopoietic Stem Cell Transplant Cope With Late Complications
NCT01305200	PHASE3	COMPLETED	Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant
NCT03862157	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
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
NCT00040846	PHASE2	COMPLETED	Alemtuzumab, Fludarabine Phosphate, and Low-Dose Total Body Irradiation Before Donor Stem Cell Transplantation in Treating Patients With Hematological 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
NCT00105001	PHASE2	COMPLETED	Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
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
NCT00462605	PHASE2	COMPLETED	MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia
NCT00509249	PHASE2	TERMINATED	Aflibercept in Treating Patients With Myelodysplastic Syndromes
NCT00530218	PHASE2	COMPLETED	Ganciclovir by Infusion and by Mouth in Treating Patients With Cytomegalovirus After Donor Bone Marrow Transplant
NCT00795769	PHASE2	COMPLETED	Ondansetron in Preventing Nausea and Vomiting in Patients Undergoing Stem Cell Transplant
NCT01056614	PHASE2	COMPLETED	Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies
NCT01093586	PHASE2	COMPLETED	Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
NCT01159067	PHASE2	TERMINATED	Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload
NCT01273766	PHASE2	COMPLETED	Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies
NCT01384513	PHASE2	COMPLETED	A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies
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
NCT01787487	PHASE2	COMPLETED	Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm
NCT01789255	PHASE2	COMPLETED	Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies
NCT01894477	PHASE2	UNKNOWN	Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia
NCT02210858	PHASE1/PHASE2	COMPLETED	Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders
NCT00025415	PHASE1	COMPLETED	Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
NCT00039091	PHASE1	TERMINATED	Monoclonal Antibody Therapy in Treating Patients With Ovarian Epithelial Cancer, Melanoma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Non-Small Cell Lung Cancer
NCT00049582	PHASE1	TERMINATED	Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
NCT00331513	PHASE1	COMPLETED	Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes
NCT00351975	PHASE1	COMPLETED	Belinostat and Azacitidine in Treating Patients With Advanced Hematologic Cancers or Other Diseases
NCT00357305	PHASE1	COMPLETED	Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders
NCT00357708	PHASE1	COMPLETED	Vorinostat and Decitabine in Treating Patients With Relapsed, Refractory, or Poor-Prognosis Hematologic Cancer or Other Diseases
NCT00890747	PHASE1	COMPLETED	Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy
NCT00988715	PHASE1	COMPLETED	Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome
NCT03566446	PHASE1	COMPLETED	CALR Exon 9 Mutant Peptide Vaccine to Patients With CALR-mutant Myeloproliferative Neoplasms
NCT03807063	PHASE1	WITHDRAWN	Rivogenlecleucel Donor Lymphocyte Immunotherapy in Treating Patients With Recurrent Blood Cancers After Stem Cell Transplant
NCT03878524	PHASE1	TERMINATED	Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
NCT01199562	Not specified	ACTIVE_NOT_RECRUITING	Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
NCT05326919	Not specified	RECRUITING	The Patient Cohort of the National Center for Precision Medicine in Leukemia
NCT07362225	Not specified	RECRUITING	MPN PROGRESSion Registry: Observational Study Tracking Symptoms, Treatments, and Disease Progression in People With Myeloproliferative Neoplasms (MPNs)
NCT00014235	Not specified	COMPLETED	Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	15
FOSCARNET	4	4
DACOMITINIB ANHYDROUS	4	3
ALEMTUZUMAB	4	2
DEFERASIROX	4	2
GANCICLOVIR	4	2
RUXOLITINIB	4	2
AFATINIB	4	1
BELINOSTAT	4	1
BICALUTAMIDE	4	1
BUSULFAN	4	1
COBIMETINIB	4	1
COPANLISIB	4	1
DAROLUTAMIDE	4	1
ENASIDENIB	4	1
ENTRECTINIB	4	1
IDELALISIB	4	1
LITHIUM CARBONATE	4	1
LORLATINIB	4	1
NERATINIB	4	1
PALIFERMIN	4	1
PONATINIB	4	1
PRAVASTATIN SODIUM	4	1
TREOSULFAN	4	1
VALGANCICLOVIR	4	1
VISMODEGIB	4	1
ENTINOSTAT	3	1
PEVONEDISTAT	3	1
TIPIFARNIB	3	1
RIMIDUCID	2	1