Lymphoid leukemia

Summary

Lymphoid leukemia (MONDO:0005402) is a cancer with 2 cohort genes (67 GWAS associations across 17 studies; 2 CIViC-evidence somatic drivers) and 47 clinical trials. Molecularly, ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation confers sensitivity to Pemigatinib in Lymphoid Leukemia (CIViC Level A). Top therapeutic interventions include acalabrutinib, cholecalciferol, and copanlisib.

At a glance

• Classification: Cancer
• Cohort genes: 2
• GWAS associations: 67
• Clinical trials: 47
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	lymphoid leukemia
Mondo ID	MONDO:0005402
EFO	EFO:0004289
MeSH	D007945
DOID	DOID:1037, DOID:10747
ICD-10-CM	C91
NCIT	C7539
SNOMED CT	188726003
UMLS	C0023448
MedGen	9728
GARD	0024179
Is cancer (heuristic)	yes

Also known as: leukemia, LYMPHOCYTIC, malignant · lymphocytic leukemia · lymphogenous leukaemia · lymphogenous leukemia · lymphoid leukaemia (disease) · lymphoid leukemia · lymphoid leukemia (disease) · subacute lymphoid leukaemia · subacute lymphoid leukemia

Data availability: 67 GWAS associations (17 studies) · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

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 › leukemia › lymphoid leukemia

Related subtypes (11): chronic leukemia, chronic erythremia, testicular leukemia, central nervous system leukemia, aleukemic leukemia, splenic manifestation of leukemia, childhood leukemia, monocytic leukemia, myeloid leukemia, acute leukemia, mast cell leukemia

Subtypes (3): acute lymphoblastic leukemia, T-cell leukemia, T-cell large granular lymphocyte leukemia

Genetics & variants

GWAS landscape

67 GWAS associations across 17 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs35923643	4e-44	GRAMD1B	A	0.45
rs7423615	6e-33	SP140	C	0.37
chr2:231110582	2e-31		C	0.37
chr9:136496196	4e-31		C	772.76
rs34855578	1e-30	SP140	C	0.33
chr15:69992458	2e-24		T	0.27
rs919054	4e-22	DRAIC	G	0.25
rs62389423	4e-22	IRF4 - EXOC2	G	0.34
rs10202539	4e-21	ACOXL	G	0.26
chr16:85927814	2e-20		C	0.27
chr6:409119	5e-20		A	0.24
rs6708784	7e-20	MIR4435-2HG	A	0.23
rs1324551	1e-19	FAS	C	0.25
rs1050979	3e-19	IRF4	A	0.23
rs375288	4e-17	RPL10AP12 - IRF8	G	0.26
chr3:169503432	6e-15		C	0.25
rs36051450	3e-14	GRAMD1B	C	1.53
rs4975538	2e-13	TERT	G	0.21
rs9811216	5e-13	ACTRT3 - MYNN	T	0.23
rs539846	5e-13	BMF	G	0.19
rs10811695	1e-12	CDKN2B-AS1 - DMRTA1	T	0.2
chr9:22338128	3e-11		C	0.19
rs4776477	4e-11	DRAIC	A	1.38
rs7705526	5e-11	TERT	C	0.18
rs78378222	2e-09	TP53	G	2.49
rs184332194	6e-09	GRIP1	?
rs187021028	9e-09	LINC01785	A	2.57
rs2316515	1e-08	IRF4	G	1.35
rs114490818	3e-08	CFAP100-DT	A	2.07
rs61965473	4e-08	SOX21-AS1 - LINC00557	T	2.03

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475612	Verma A	2024	3,177	447,521	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475613	Verma A	2024	2,845	448,087	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079642	Backman JD	2021	878	386,951	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083628	Backman JD	2021	878	386,951	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90011814	Rashkin SR	2020	852	410,350	Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts.
GCST90079125	Backman JD	2021	699	73,531	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083111	Backman JD	2021	699	73,531	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90435648	Zhou W	2018	578	404,466	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90435650	Zhou W	2018	506	404,466	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90479831	Verma A	2024	426	121,368	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	3
Tier 3: regulatory	2
Tier 4: intronic/intergenic	39

MAF distribution

Bucket	Variants
common (>=0.05)	31
low_freq (0.01-0.05)	11
rare (<0.01)	0
unknown	3

Functional consequences

Consequence	Count
intron_variant	21
unknown	7
intergenic_variant	7
non_coding_transcript_exon_variant	3
3_prime_UTR_variant	3
regulatory_region_variant	2
stop_gained	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs35923643	11	123484683	A>G	0.159	intron_variant	GRAMD1B	4e-44	Tier 4: intronic/intergenic
rs7423615	2	230252159	C>T	0.167	intron_variant	SP140	6e-33	Tier 4: intronic/intergenic
chr2:231110582				0.188			2e-31	Tier 4: intronic/intergenic
chr9:136496196							4e-31	Tier 4: intronic/intergenic
rs34855578	2	230250275	C>G	0.173	intron_variant	SP140	1e-30	Tier 4: intronic/intergenic
chr15:69992458				0.39			2e-24	Tier 4: intronic/intergenic
rs919054	15	69698198	G>A,C,T	0.375	intergenic_variant	DRAIC	4e-22	Tier 4: intronic/intergenic
rs62389423	6	421281	G>A,T	0.123	intergenic_variant	IRF4 - EXOC2	4e-22	Tier 4: intronic/intergenic
rs10202539	2	110944968	G>A	0.301	intron_variant	ACOXL	4e-21	Tier 4: intronic/intergenic
chr16:85927814				0.372			2e-20	Tier 4: intronic/intergenic
chr6:409119				0.496			5e-20	Tier 4: intronic/intergenic
rs6708784	2	111169802	A>G,T	0.451	intron_variant	MIR4435-2HG	7e-20	Tier 4: intronic/intergenic
rs1324551	10	88991759	C>A,T	0.493	non_coding_transcript_exon_variant	FAS	1e-19	Tier 4: intronic/intergenic
rs1050979	6	410417	A>C,G	0.416	3_prime_UTR_variant	IRF4	3e-19	Tier 2: splice/UTR
rs375288	16	85894265	G>A,C,T	0.39	regulatory_region_variant	RPL10AP12 - IRF8	4e-17	Tier 3: regulatory
chr3:169503432				0.267			6e-15	Tier 4: intronic/intergenic
rs36051450	11	123474251	T>C	0.05	intron_variant	GRAMD1B	3e-14	Tier 4: intronic/intergenic
rs4975538	5	1280715	G>A,C,T	0.359	intron_variant	TERT	2e-13	Tier 4: intronic/intergenic
rs9811216	3	169769713	T>C,G	0.268	non_coding_transcript_exon_variant	ACTRT3 - MYNN	5e-13	Tier 4: intronic/intergenic
rs539846	15	40105735	G>A,C,T	0.437	intron_variant	BMF	5e-13	Tier 4: intronic/intergenic
rs10811695	9	22363443	T>A,C,G	0.484	intron_variant	CDKN2B-AS1 - DMRTA1	1e-12	Tier 4: intronic/intergenic
chr9:22338128				0.481			3e-11	Tier 4: intronic/intergenic
rs4776477	15	69732068	A>G,T	0.05	intergenic_variant	DRAIC	4e-11	Tier 4: intronic/intergenic
rs7705526	5	1285859	C>A,G,T	0.337	intron_variant	TERT	5e-11	Tier 4: intronic/intergenic
rs78378222	17	7668434	T>A,G	0.012	3_prime_UTR_variant	TP53	2e-09	Tier 2: splice/UTR
rs184332194	12	66941159	G>A,C,T		intergenic_variant	GRIP1	6e-09	Tier 4: intronic/intergenic
rs187021028	19	22616454	T>A	0.014	non_coding_transcript_exon_variant	LINC01785	9e-09	Tier 4: intronic/intergenic
rs2316515	6	410848	A>G	0.05	3_prime_UTR_variant	IRF4	1e-08	Tier 2: splice/UTR
rs114490818	3	126380258	G>A	0.022	intron_variant	CFAP100-DT	3e-08	Tier 4: intronic/intergenic
rs61965473	13	94919532	C>T	0.023	intergenic_variant	SOX21-AS1 - LINC00557	4e-08	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
JAK2	Act	ALL,AML,BLADDER,BRCA,NSCLC	CIViC #28

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
JAK2	Orphanet:131	Budd-Chiari syndrome
JAK2	Orphanet:3318	Essential thrombocythemia
JAK2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
JAK2	Orphanet:71493	Familial thrombocytosis
JAK2	Orphanet:729	Polycythemia vera
JAK2	Orphanet:824	Primary myelofibrosis

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
JAK2	HGNC:6192	ENSG00000096968	O60674	Tyrosine-protein kinase JAK2	civic_evidence

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
JAK2	Tyrosine-protein kinase JAK2	Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications.

Protein-family classification

Druggable: 2 · 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	2	27.7×	0.001

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
JAK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
buccal mucosa cell	1
stromal cell of endometrium	1
blood vessel layer	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
JAK2	272	ubiquitous	marker	calcaneal tendon, monocyte, blood vessel layer

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JAK2	6,197
FGFR1	5,693

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
JAK2	O60674	164
FGFR1	P11362	83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 87. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by FGFR1 amplification mutants	1	2855.0×	0.009	FGFR1
FGFR1c and Klotho ligand binding and activation	1	1427.5×	0.009	FGFR1
Signaling by plasma membrane FGFR1 fusions	1	1427.5×	0.009	FGFR1
Erythropoietin activates Phospholipase C gamma (PLCG)	1	815.7×	0.009	JAK2
Erythropoietin activates STAT5	1	815.7×	0.009	JAK2
Interleukin-6 family signaling	1	713.8×	0.009	JAK2
IFNG signaling activates MAPKs	1	713.8×	0.009	JAK2
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	713.8×	0.009	FGFR1
FGFR1b ligand binding and activation	1	634.4×	0.009	FGFR1
Interleukin-23 signaling	1	634.4×	0.009	JAK2
MAPK1 (ERK2) activation	1	571.0×	0.009	JAK2
Signaling by KIT in disease	1	571.0×	0.009	JAK2
MAPK3 (ERK1) activation	1	519.1×	0.009	JAK2
Signaling by Leptin	1	519.1×	0.009	JAK2
Signaling by Erythropoietin	1	519.1×	0.009	JAK2
Interleukin-27 signaling	1	519.1×	0.009	JAK2
Interleukin-6 signaling	1	475.8×	0.009	JAK2
Signaling by activated point mutants of FGFR1	1	475.8×	0.009	FGFR1
Interleukin-35 Signalling	1	475.8×	0.009	JAK2
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	475.8×	0.009	JAK2
RAF/MAP kinase cascade	2	61.1×	0.009	FGFR1, JAK2
Regulation of IFNG signaling	1	407.9×	0.009	JAK2
Prolactin receptor signaling	1	380.7×	0.009	JAK2
FGFR1c ligand binding and activation	1	380.7×	0.009	FGFR1
Erythropoietin activates RAS	1	380.7×	0.009	JAK2
Phospholipase C-mediated cascade: FGFR1	1	335.9×	0.009	FGFR1
RAF-independent MAPK1/3 activation	1	317.2×	0.009	JAK2
Interleukin-2 family signaling	1	317.2×	0.009	JAK2
IL-6-type cytokine receptor ligand interactions	1	317.2×	0.009	JAK2
Signaling by CSF3 (G-CSF)	1	285.5×	0.010	JAK2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of cell differentiation	2	267.5×	0.002	FGFR1, JAK2
nuclear receptor-mediated mineralocorticoid signaling pathway	1	8426.0×	0.003	JAK2
symbiont-induced defense-related programmed cell death	1	8426.0×	0.003	JAK2
interleukin-35-mediated signaling pathway	1	8426.0×	0.003	JAK2
vitamin D3 metabolic process	1	4213.0×	0.003	FGFR1
response to interleukin-12	1	4213.0×	0.003	JAK2
positive regulation of growth factor dependent skeletal muscle satellite cell proliferation	1	4213.0×	0.003	JAK2
positive regulation of mitotic cell cycle DNA replication	1	4213.0×	0.003	FGFR1
regulation of postsynapse to nucleus signaling pathway	1	4213.0×	0.003	JAK2
positive regulation of parathyroid hormone secretion	1	4213.0×	0.003	FGFR1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1	4213.0×	0.003	FGFR1
protein autophosphorylation	2	145.3×	0.003	FGFR1, JAK2
positive regulation of MAPK cascade	2	80.6×	0.003	FGFR1, JAK2
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	78.4×	0.003	FGFR1, JAK2
regulation of phosphate transport	1	2808.7×	0.003	FGFR1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	2808.7×	0.003	FGFR1
regulation of lateral mesodermal cell fate specification	1	2808.7×	0.003	FGFR1
positive regulation of growth hormone receptor signaling pathway	1	2808.7×	0.003	JAK2
ventricular zone neuroblast division	1	2106.5×	0.003	FGFR1
collagen-activated signaling pathway	1	2106.5×	0.003	JAK2
granulocyte-macrophage colony-stimulating factor signaling pathway	1	2106.5×	0.003	JAK2
activation of Janus kinase activity	1	2106.5×	0.003	JAK2
negative regulation of fibroblast growth factor production	1	2106.5×	0.003	FGFR1
positive regulation of phospholipase activity	1	1685.2×	0.003	FGFR1
regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling	1	1685.2×	0.003	FGFR1
diphosphate metabolic process	1	1685.2×	0.003	FGFR1
post-embryonic hemopoiesis	1	1404.3×	0.003	JAK2
cellular response to interleukin-3	1	1404.3×	0.003	JAK2
interleukin-5-mediated signaling pathway	1	1404.3×	0.003	JAK2
interleukin-23-mediated signaling pathway	1	1404.3×	0.003	JAK2

Therapeutics

Drugs indicated for this disease

7 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Asparaginase	Approved (phase 4)
Blinatumomab	Approved (phase 4)
Clofarabine	Approved (phase 4)
Cytarabine	Approved (phase 4)
Dasatinib Anhydrous	Approved (phase 4)
Inotuzumab Ozogamicin	Approved (phase 4)
Pegaspargase	Approved (phase 4)
Carvedilol	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Enalapril	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Hydrocortisone	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Mitoxantrone	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Thioguanine	Phase 3 (in late-stage trials)
Vincristine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alemtuzumab, Azacitidine, Bevacizumab, Brexucabtagene Autoleucel, Crisantaspase, Daratumumab, Daunorubicin, Doxorubicin, Duvelisib, Fludarabine, Fludarabine Phosphate, Ibrutinib, Imatinib, Lenalidomide, Obinutuzumab, Ofatumumab, Prednisolone, TOSITUMOMAB 131I, Thalidomide, Tositumomab, Venetoclax, Zanubrutinib.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
FGFR1	PONATINIB
JAK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
JAK2	100	4
FGFR1	93	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR1, JAK2
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1, JAK2
FEDRATINIB	4	FGFR1, JAK2
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1, JAK2
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1, JAK2
INFIGRATINIB PHOSPHATE	4	FGFR1, JAK2
INFIGRATINIB	4	FGFR1, JAK2
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1, JAK2
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1, JAK2
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1, JAK2
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1, JAK2
SUNITINIB	4	FGFR1, JAK2
DASATINIB	4	FGFR1, JAK2
MIDOSTAURIN	4	FGFR1, JAK2
RUXOLITINIB	4	JAK2
TOFACITINIB	4	JAK2
MOMELOTINIB	4	JAK2
RUXOLITINIB PHOSPHATE	4	JAK2
DABRAFENIB	4	JAK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
JAK2	2,018	Binding:1911, Functional:51, ADMET:48, Unclassified:4, Toxicity:4
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
JAK2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
FGFR1	1,465
JAK2	2,018

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
PONATINIB	4	FGFR1, JAK2
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1, JAK2
FEDRATINIB	4	FGFR1, JAK2
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1, JAK2
SORAFENIB	4	FGFR1
NICLOSAMIDE	4	FGFR1, JAK2
INFIGRATINIB PHOSPHATE	4	FGFR1, JAK2
INFIGRATINIB	4	FGFR1, JAK2
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1, JAK2
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1, JAK2
ERDAFITINIB	4	FGFR1
UPADACITINIB	4	FGFR1, JAK2
FUTIBATINIB	4	FGFR1
PAZOPANIB	4	FGFR1, JAK2
SUNITINIB	4	FGFR1, JAK2
DASATINIB	4	FGFR1, JAK2
MIDOSTAURIN	4	FGFR1, JAK2
RUXOLITINIB	4	JAK2
TOFACITINIB	4	JAK2
MOMELOTINIB	4	JAK2
RUXOLITINIB PHOSPHATE	4	JAK2
DABRAFENIB	4	JAK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	FGFR1, JAK2
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: 47.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	19
Not specified	11
PHASE1	7
PHASE1/PHASE2	5
PHASE3	3
PHASE2/PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04608318	PHASE3	ACTIVE_NOT_RECRUITING	Ibrutinib Monotherapy Versus Fixed-duration Venetoclax Plus Obinutuzumab Versus Fixed-duration Ibrutinib Plus Venetoclax in Patients With Previously Untreated Chronic Lymphocytic Leukaemia (CLL)
NCT00469729	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy
NCT00517218	PHASE3	WITHDRAWN	This Study is Being Performed to Evaluate the Effect of Genasense on the Efficacy and the Safety of Rituximab/Fludarabine Combination Treatment in Previously Untreated Subjects With Chronic Lymphocyctic Leukemia(CLL)
NCT01518959	PHASE3	TERMINATED	The Effect of 25-OH-Vitamin-D3 Substitution in Patients With Malignant and Immune-hematologic Diseases
NCT03766763	PHASE2	ACTIVE_NOT_RECRUITING	Preemptive Therapy for High Risk Chronic Lymphoid Leukemia Stage A
NCT03852407	PHASE2	RECRUITING	Allogeneic Hematopoietic Cell Transplantation From HLA-matched Donor After Flu-Mel-PTCy Versus Flu-Mel-ATG Reduced-intensity Conditioning
NCT04515238	PHASE2	ACTIVE_NOT_RECRUITING	Sequential Regimen of Bendamustine Followed by Obinutuzumab (GA101), Zanubrutinib (BGB-3111) and Venetoclax (ABT-199) in Patients With Relapsed/Refractory CLL
NCT05366218	PHASE1/PHASE2	RECRUITING	Tafasitamab (MOR00208) in Pediatric Patients With Relapsed or Refractory Acute B Lineage Leukemia
NCT07070219	PHASE1/PHASE2	RECRUITING	A Study of CTD402 in T-ALL/LBL Patients
NCT07292272	PHASE2	RECRUITING	Halt Aging in Survivors of Blood Cancers
NCT07566364	PHASE2	NOT_YET_RECRUITING	Phase 2 Study Of Mosunetuzumab In Patients With Chronic Lymphocytic Leukemia With Positive MRD
NCT00406809	PHASE1/PHASE2	COMPLETED	A Study of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies
NCT00609869	PHASE2	COMPLETED	Lenalidomide in Comb w/Rituximab for Pts w/CD5+/CD20+ Hem Malignancies Who Relapse/Progress After Rituximab
NCT00683046	PHASE2	COMPLETED	T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00801580	PHASE2	UNKNOWN	My-HyperCVAD in the Treatment of Relapsed Refractory Adult Acute Lymphoid Leukemia
NCT00935792	PHASE1/PHASE2	COMPLETED	Everolimus and Alemtuzumab in Treating Patients With Recurrent Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT01754857	PHASE2	COMPLETED	Bendamustine and Rituximab Induction Therapy and Maintenance Rituximab and Lenalidomide in Previously Untreated CLL/SLL
NCT02462265	PHASE2	SUSPENDED	Oshadi D & Oshadi R Combined With Salvage Chemotherapy for Relapsed Acute Myeloid Leukemia or Lymphoid Leukemia Patients
NCT02481297	PHASE2	COMPLETED	Lirilumab With Rituximab for Relapsed, Refractory or High-risk Untreated Chronic Lymphocytic Leukemia (CLL) Patients
NCT02593123	PHASE2	COMPLETED	Adoptive Immunotherapy in Relapsed Hematological Malignancy: Early GVHD Prophylaxis
NCT03575325	PHASE2	COMPLETED	Vyxeos(CPX-351) in Adults w R/R Acute Lymphoblastic Leukemia
NCT03613727	PHASE2	COMPLETED	Therapeutic Use of Intravenous Vitamin C in Allogeneic Stem Cell Transplant Recipients
NCT03787264	PHASE2	COMPLETED	Sequential Regimen of Bendamustin-Debulking Followed by Obinutuzumab, Acalabrutinib and Venetoclax in Patients With Relapsed/Refractory CLL
NCT03804372	PHASE2	TERMINATED	The Incidence of Hepatitis B in Diffuse Large B-Cell Lymphoma/Chronic Lymphoid Leukemia HBsAg-positive Treated With Rituximab, Chemotherapy and Tenofovir Alafenamide
NCT04155840	PHASE2	TERMINATED	Bendamustine and Rituximab in Combination With Copanlisib for the Treatment of Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
NCT04340154	PHASE2	TERMINATED	Study of Sequential CAR-T Cell Treating Leukemia Children
NCT04883749	PHASE2	COMPLETED	Efficacy of Acalabrutinib in Very Old or Frail Patients With Treatment-naïve or Relapsed/Refractory CLL
NCT05272813	PHASE1/PHASE2	TERMINATED	A Study to Investigate the Efficacy and Safety of MS-553 in CLL/SLL
NCT02735083	PHASE1	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Long-term Safety of Patients With Advanced Lymphoid Leukemia Who Have Been Previously Administered With UCART19
NCT03219450	PHASE1	RECRUITING	A Personalized Neoantigen Cancer Vaccine in Treatment Naïve, Asymptomatic Patients With IGHV Unmutated CLL.
NCT05507827	PHASE1	ACTIVE_NOT_RECRUITING	Myeloablative Conditioning Orca-T & Allogeneic Donor-Derived CD19/CD22-CAR TCells in B-Cell ALL
NCT00788684	PHASE1	COMPLETED	Safety Study of ABT-263 in Combination With Rituximab in Lymphoid Cancers
NCT01643603	PHASE1	TERMINATED	Dasatinib for Immune Modulation After Donor Stem Cell Transplant for Hematologic Malignancies
NCT02556892	PHASE1	COMPLETED	A Study of Bruton’s Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Treatment-naive Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT05065866	PHASE1	COMPLETED	Duvelisib in Combination With BMS-986345 in Lymphoid Malignancy
NCT00013533	EARLY_PHASE1	COMPLETED	Pilot Study of Non-Myeloablative, HLA-Matched Allogeneic Stem Cell Transplantation for Pediatric Hematopoietic Malignancies
NCT05865301	Not specified	RECRUITING	Outcomes in Pediatric and Young Adult B-Cell Malignancies After Commercially Available Immunotherapy
NCT05871008	Not specified	ACTIVE_NOT_RECRUITING	Integrated Actionable Aging Assessment for Cancer Patients Pilot
NCT06343090	Not specified	RECRUITING	Clinical Trial of CD19 and CD22 CAR Sequential Therapy Versus Single CD19 CAR Bridging to HSCT for r/r B-ALL Patients
NCT06389305	Not specified	RECRUITING	CIK Cell Therapy for Relapsed or Refractory Acute B-Lymphoblastic Leukemia: Prognostic Impact on Patients With Early CAR-T Cell Dysfunction

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ACALABRUTINIB	4	2
CHOLECALCIFEROL	4	1
COPANLISIB	4	1
DUVELISIB	4	1
IBRUTINIB	4	1
MITOXANTRONE	4	1
MOSUNETUZUMAB	4	1
OBINUTUZUMAB	4	1
TAFASITAMAB	4	1
TENOFOVIR ALAFENAMIDE	4	1
VENETOCLAX	4	1
ZANUBRUTINIB	4	1
NAVITOCLAX	3	2
OBLIMERSEN SODIUM	3	1
LIRILUMAB	2	1
OBLIMERSEN	2	1
CHEMBL4747506	0	2
CHEMBL5187554	0	2
CHEMBL5276925	0	2
CHEMBL3647964	0	1
CHEMBL3970001	0	1
CHEMBL4466205	0	1
CHEMBL5193128	0	1
CHEMBL3805348	0	1
CHEMBL4538684	0	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
ZMYM2::FGFR1 Fusion OR BCR::FGFR1 Fusion OR CEP43::FGFR1 Fusion OR TRIM24::FGFR1 Fusion OR FGFR1 Translocation	Pemigatinib	Sensitivity/Response	CIViC A	EID12241