Chronic myeloid leukemia

Summary

Chronic myeloid leukemia (MONDO:0011996) is a cancer with 25 cohort genes (2 GWAS associations across 6 studies; 16 CIViC-evidence somatic drivers; 22 ClinVar predisposition records) and 652 clinical trials. The dominant Reactome pathway is Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (5 cohort genes). Molecularly, BCR::ABL1 Fusion confers sensitivity to Asciminib in Chronic Myeloid Leukemia (CIViC Level A); 335 further subtype–drug associations are mapped below. Top therapeutic interventions include imatinib, nilotinib, and dasatinib anhydrous.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 25
• GWAS associations: 2
• ClinVar variants: 22
• Phenotypes (HPO): 11
• Clinical trials: 652
• Precision-medicine evidence (CIViC): 336 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	1.25	Europe	Validated
Lifetime Prevalence	1-9 / 100 000	5.63	Europe	Validated
Point prevalence	1-9 / 100 000	6	Europe	Validated
Annual incidence	1-9 / 100 000	1.25	France	Validated
Annual incidence	1-9 / 100 000	1.7	United States	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0005547	Myeloproliferative disorder	Obligate (100%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0001871	Abnormality of blood and blood-forming tissues	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001894	Thrombocytosis	Frequent (30-79%)
HP:0001911	Abnormality of granulocytes	Frequent (30-79%)
HP:0001912	Abnormality of basophils	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0001974	Leukocytosis	Frequent (30-79%)
HP:0004396	Poor appetite	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	chronic myeloid leukemia
Mondo ID	MONDO:0011996
EFO	EFO:0000339
OMIM	608232
Orphanet	521
DOID	DOID:0081088, DOID:8552
NCIT	C3174
UMLS	C0279543
MedGen	75993
GARD	0006105
MedDRA	10009013
Is cancer (heuristic)	yes

Also known as: BCR-ABL Positive chronic myelogenous leukaemia · BCR-ABL Positive chronic myelogenous leukemia · chronic granulocytic leukemia · chronic myelocytic leukaemia · chronic myelocytic leukemia · chronic myelogenous leukaemia (CML) · chronic myelogenous leukemia · chronic myelogenous leukemia (CML) · chronic myelogenous leukemia, BCR-ABL1 Positive · chronic myelogenous leukemias · chronic myeloid leukemia · CML · CML - chronic myelogenous leukaemia · CML - chronic myelogenous leukemia · hematopoeitic - chronic myelocytic leukaemia (CML) · hematopoeitic - chronic myelocytic leukemia (CML) · leukimia, chronic myeloid · myeloid leukemia, chronic

Data availability: 22 ClinVar variants · 2 GWAS associations (6 studies) · 7,587 cell lines.

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 › myeloid leukemia › chronic myeloid leukemia

Related subtypes (3): atypical chronic myeloid leukemia, BCR-ABL1 negative, acute myeloid leukemia, Philadelphia-positive myelogenous leukemia

Subtypes (3): blast phase chronic myelogenous leukemia, BCR-ABL1 positive, familial chronic myelocytic leukemia-like syndrome, leukemia, myeloid, accelerated-phase

Genetics & variants

GWAS landscape

2 GWAS associations across 6 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4795519	1e-12	TUFMP1 - RPL34P31	C	1.85
rs4869742	2e-06	CCDC170	T	1.67

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90481547	Verma A	2024	734	450,582	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST001063	Kim DH	2011	201	0	A genome-wide association study identifies novel loci associated with susceptibility to chronic myeloid leukemia.
GCST90435653	Zhou W	2018	153	404,466	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90042759	Jiang L	2021	144	456,204	A generalized linear mixed model association tool for biobank-scale data.
GCST90041913	Jiang L	2021	112	456,164	A generalized linear mixed model association tool for biobank-scale data.
GCST90043913	Jiang L	2021	110	456,238	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	2

MAF distribution

Bucket	Variants
common (>=0.05)	2
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4795519	17	27214252	A>C,G	0.48	intergenic_variant	TUFMP1 - RPL34P31	1e-12	Tier 4: intronic/intergenic
rs4869742	6	151586613	C>A,G,T	0.23	intron_variant	CCDC170	2e-06	Tier 4: intronic/intergenic

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 5 benign/likely benign, 4 pathogenic, 3 not provided, 2 conflicting classifications of pathogenicity, 1 likely pathogenic; association, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
12628	NM_005157.6(ABL1):c.931T>C (p.Phe311Leu)	ABL1	Pathogenic	no assertion criteria provided
12629	NM_005157.6(ABL1):c.1052T>C (p.Met351Thr)	ABL1	Pathogenic	no assertion criteria provided
12583	NM_004985.5(KRAS):c.35G>T (p.Gly12Val)	KRAS	Pathogenic	criteria provided, multiple submitters, no conflicts
40468	NM_002524.5(NRAS):c.34G>T (p.Gly12Cys)	NRAS	Pathogenic	criteria provided, single submitter
12624	NM_005157.6(ABL1):c.944C>T (p.Thr315Ile)	ABL1	Likely pathogenic; association	criteria provided, multiple submitters, no conflicts
3596486	NM_005157.6(ABL1):c.2456G>A (p.Arg819Gln)	ABL1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
376004	NM_012433.4(SF3B1):c.2098A>G (p.Lys700Glu)	SF3B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3596485	NM_005157.6(ABL1):c.1726G>C (p.Glu576Gln)	ABL1	Uncertain significance	criteria provided, single submitter
1206149	NM_004327.4(BCR):c.3275_3278dup (p.Val1094fs)	BCR	Uncertain significance	criteria provided, multiple submitters, no conflicts
625894	NM_004327.4(BCR):c.2356G>A (p.Ala786Thr)	BCR	Uncertain significance	criteria provided, single submitter
625895	NM_004327.4(BCR):c.685C>T (p.Pro229Ser)	BCR	Uncertain significance	criteria provided, single submitter
626065	NM_004327.4(BCR):c.1149C>T (p.Pro383=)	BCR	Uncertain significance	criteria provided, single submitter
1710502	NM_006060.6(IKZF1):c.1474T>G (p.Cys492Gly)	IKZF1	Uncertain significance	no assertion criteria provided
1594971	NM_005157.6(ABL1):c.2035T>G (p.Ser679Ala)	ABL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
1599197	NM_005157.6(ABL1):c.822+16C>G	ABL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
713869	NM_005157.6(ABL1):c.1899C>T (p.Ala633=)	ABL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
719810	NM_005157.6(ABL1):c.249T>G (p.Thr83=)	ABL1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
723652	NM_005157.6(ABL1):c.2117G>T (p.Gly706Val)	ABL1	Likely benign	criteria provided, multiple submitters, no conflicts
780633	NM_004327.4(BCR):c.606C>T (p.Ser202=)	BCR	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
143220	NM_004327.4(BCR):c.2699A>G (p.Asn900Ser)	BCR	not provided	no classification provided
143221	NM_004327.4(BCR):c.2707+21G>T	BCR	not provided	no classification provided
143222	NM_004327.4(BCR):c.2750T>A (p.Val917Asp)	LOC107963955	not provided	no classification provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 81 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ABL1	LoF	UCEC	CIViC #4
SETBP1	Act	ACC	CIViC #10024
EGFR	Act	BRCA,COADREAD,GB,GBM,HGGNOS,LGGNOS,LUAD,LUSC,NSCLC,PAST,PCM,READ,SIC	CIViC #19
ABCB1			CIViC #4244
JAK2	Act	ALL,AML,BLADDER,BRCA,NSCLC	CIViC #28
KIT	Act	AML,GIST,MEL,MGCT	CIViC #29
LYN	Act	CLLSLL,DLBCLNOS	CIViC #3359
PDGFRA	Act	CSCC,GB,GBM,HGGNOS,LGGNOS,LUSC,PAST	CIViC #38
BCL2L11			CIViC #7953
RET	Act	ANGS,MEL,NSCLC,PGNG,SOFT_TISSUE,WDTC	CIViC #42
BCR	Act	BL,CLLSLL,DLBCLNOS,LUSC,NHL,WDTC
SF3B1	Act	AML,BLCA,BRCA,CHOL,CLLSLL,HCC,LUNG,MBL,MEL,PAAD,PCM,PRAD,SKCM,UM	CIViC #44
IKZF1	Act	AML,ANSC,SKCM	CIViC #73
ESR1	Act	BRCA,LUSC,MEL,UCEC	CIViC #21
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
NRAS	Act	ALL,AML,ANGS,CHOL,CLLSLL,COAD,COADREAD,GBM,HCC,LGGNOS,LUAD,LUSC,MEL,MGCT,NPC,OVT,PCM,PROSTATE,SKCM,THYM,UCEC,WDTC	CIViC #36

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ABL1	Orphanet:521	Chronic myeloid leukemia
ABL1	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
ABL1	Orphanet:643503	Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome
ABL1	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
SETBP1	Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome
SETBP1	Orphanet:798	Schinzel-Giedion syndrome
EGFR	Orphanet:251576	Gliosarcoma
EGFR	Orphanet:251579	Giant cell glioblastoma
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
KIT	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
KIT	Orphanet:158766	Typical urticaria pigmentosa
KIT	Orphanet:158769	Plaque-form urticaria pigmentosa
KIT	Orphanet:158772	Nodular urticaria pigmentosa
KIT	Orphanet:158775	Smoldering systemic mastocytosis
KIT	Orphanet:158778	Isolated bone marrow mastocytosis
KIT	Orphanet:280785	Bullous diffuse cutaneous mastocytosis
KIT	Orphanet:280794	Pseudoxanthomatous diffuse cutaneous mastocytosis
KIT	Orphanet:2884	Piebaldism
KIT	Orphanet:44890	Gastrointestinal stromal tumor
KIT	Orphanet:566393	Acute mast cell leukemia
KIT	Orphanet:566396	Chronic mast cell leukemia
KIT	Orphanet:79455	Cutaneous mastocytoma
KIT	Orphanet:842	Testicular seminomatous germ cell tumor
KIT	Orphanet:90389	Telangiectasia macularis eruptiva perstans
KIT	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
KIT	Orphanet:98834	Acute myeloblastic leukemia with maturation
KIT	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
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
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome
BCR	Orphanet:261330	Distal 22q11.2 microdeletion syndrome
BCR	Orphanet:521	Chronic myeloid leukemia

Cohort genes → proteins

25 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	9
civic_only	9
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ABL1	HGNC:76	ENSG00000097007	P00519	Tyrosine-protein kinase ABL1	clinvar,civic_evidence
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	civic_evidence
EGFR	HGNC:3236	ENSG00000146648	P00533	Epidermal growth factor receptor	civic_evidence
ABCB1	HGNC:40	ENSG00000085563	P08183	ATP-dependent translocase ABCB1	civic_evidence
JAK2	HGNC:6192	ENSG00000096968	O60674	Tyrosine-protein kinase JAK2	civic_evidence
KIT	HGNC:6342	ENSG00000157404	P10721	Mast/stem cell growth factor receptor Kit	civic_evidence
LYN	HGNC:6735	ENSG00000254087	P07948	Tyrosine-protein kinase Lyn	civic_evidence
PDGFRA	HGNC:8803	ENSG00000134853	P16234	Platelet-derived growth factor receptor alpha	civic_evidence
BCL2L11	HGNC:994	ENSG00000153094	O43521	Bcl-2-like protein 11	civic_evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	civic_evidence
BCR	HGNC:1014	ENSG00000186716	P11274	Breakpoint cluster region protein	clinvar
SF3B1	HGNC:10768	ENSG00000115524	O75533	Splicing factor 3B subunit 1	clinvar
SF3B2	HGNC:10769	ENSG00000087365	Q13435	Splicing factor 3B subunit 2	clinvar
IKZF1	HGNC:13176	ENSG00000185811	Q13422	DNA-binding protein Ikaros	clinvar
DCPH1	HGNC:17872	ENSG00000146476	Q9H993	Damage-control phosphatase 1	gwas
WSB1	HGNC:19221	ENSG00000109046	Q9Y6I7	WD repeat and SOCS box-containing protein 1	gwas
ZBTB2	HGNC:20868	ENSG00000181472	Q8N680	Zinc finger and BTB domain-containing protein 2	gwas
MTHFD1L	HGNC:21055	ENSG00000120254	Q6UB35	Monofunctional C1-tetrahydrofolate synthase, mitochondrial	gwas
RMND1	HGNC:21176	ENSG00000155906	Q9NWS8	Required for meiotic nuclear division protein 1 homolog	gwas
CCDC170	HGNC:21177	ENSG00000120262	Q8IYT3	Coiled-coil domain-containing protein 170	gwas
FAM27E5	HGNC:32410	ENSG00000178130		family with sequence similarity E5	gwas
ESR1	HGNC:3467	ENSG00000091831	P03372	Estrogen receptor	gwas
AKAP12	HGNC:370	ENSG00000131016	Q02952	A-kinase anchor protein 12	gwas
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	clinvar
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ABL1	Tyrosine-protein kinase ABL1	Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autopha…
EGFR	Epidermal growth factor receptor	Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses.
ABCB1	ATP-dependent translocase ABCB1	Translocates drugs and phospholipids across the membrane.
JAK2	Tyrosine-protein kinase JAK2	Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications.
KIT	Mast/stem cell growth factor receptor Kit	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell develo…
LYN	Tyrosine-protein kinase Lyn	Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integr…
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.
BCL2L11	Bcl-2-like protein 11	Induces apoptosis and anoikis.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
BCR	Breakpoint cluster region protein	Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
SF3B1	Splicing factor 3B subunit 1	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
SF3B2	Splicing factor 3B subunit 2	Component of the 17S U2 SnRNP complex of the spliceosome, a large ribonucleoprotein complex that removes introns from transcribed pre-mRNAs.
IKZF1	DNA-binding protein Ikaros	Transcription regulator of hematopoietic cell differentiation.
DCPH1	Damage-control phosphatase 1	Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate.
WSB1	WD repeat and SOCS box-containing protein 1	Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
ZBTB2	Zinc finger and BTB domain-containing protein 2	May be involved in transcriptional regulation.
MTHFD1L	Monofunctional C1-tetrahydrofolate synthase, mitochondrial	May provide the missing metabolic reaction required to link the mitochondria and the cytoplasm in the mammalian model of one-carbon folate metabolism complementing thus the enzymatic activities of MTHFD2.
RMND1	Required for meiotic nuclear division protein 1 homolog	Required for mitochondrial translation, possibly by coordinating the assembly or maintenance of the mitochondrial ribosome.
CCDC170	Coiled-coil domain-containing protein 170	Plays a role in Golgi-associated microtubules organization and stabilization.
ESR1	Estrogen receptor	Nuclear hormone receptor.
AKAP12	A-kinase anchor protein 12	Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.

Protein-family classification

Druggable: 11 · Difficult: 4 · Unknown: 10 · Druggable fraction: 0.44

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	7	7.8×	1e-04
Nuclear receptor	1	15.4×	0.220
Transporter	1	3.1×	0.645
Scaffold/PPI	2	1.4×	0.750
Enzyme (other)	2	1.0×	0.880
Transcription factor	2	0.7×	0.961
Other/Unknown	10	0.7×	0.963

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ABL1	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif
EGFR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ABCB1	Transporter	yes	7.6.2.2	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
JAK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
KIT	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
LYN	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
PDGFRA	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
BCL2L11	Other/Unknown	no		Apoptosis_Bim_N, Bcl-x_interacting_BH3_dom, Bcl-2-like_11
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
BCR	Scaffold/PPI	no		C2_dom, RhoGAP_dom, DH_dom
SF3B1	Other/Unknown	no		ARM-like, SF3b_su1, ARM-type_fold
SF3B2	Other/Unknown	no		SAP_dom, PSP_pro-rich, DUF382
IKZF1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
DCPH1	Other/Unknown	no		ARMT1-like_metal-bd, ARMT-1-like_metal-bd_sf, ARMT1
WSB1	Scaffold/PPI	no		SOCS_box, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
ZBTB2	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
MTHFD1L	Enzyme (other)	yes	6.3.4.3	Formate_THF_ligase, THF_DH/CycHdrlase, Formate_THF_ligase_CS
RMND1	Other/Unknown	no		DUF155, RMD1/Sad1-interacting
CCDC170	Other/Unknown	no		CCDC170-like
FAM27E5	Other/Unknown	no
ESR1	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
AKAP12	Other/Unknown	no		AKAP_WSK, RII-bd_1, AKAP12
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type

Expression context

Cohort genes with no expression data: 0.

23 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)	25
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	4
monocyte	3
secondary oocyte	3
gingival epithelium	2
nipple	2
calcaneal tendon	2
lateral nuclear group of thalamus	2
oocyte	2
leukocyte	2
mononuclear cell	2
tibia	2
palpebral conjunctiva	2
dorsal root ganglion	2
epithelium of nasopharynx	2
frontal pole	1
middle frontal gyrus	1
paraflocculus	1
buccal mucosa cell	1
caput epididymis	1
gingiva	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ABL1	283	ubiquitous	marker	frontal pole, paraflocculus, middle frontal gyrus
SETBP1	280	ubiquitous	marker	ventricular zone, buccal mucosa cell, caput epididymis
EGFR	285	ubiquitous	marker	nipple, gingiva, gingival epithelium
ABCB1	232	broad	marker	right adrenal gland, right adrenal gland cortex, left adrenal gland cortex
JAK2	272	ubiquitous	marker	calcaneal tendon, monocyte, blood vessel layer
KIT	263	broad	marker	lateral nuclear group of thalamus, secondary oocyte, oocyte
LYN	263	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
PDGFRA	289	ubiquitous	marker	tibia, decidua, synovial joint
BCL2L11	256	ubiquitous	marker	sperm, palpebral conjunctiva, male germ cell
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
BCR	275	ubiquitous	marker	nucleus accumbens, caudate nucleus, putamen
SF3B1	295	ubiquitous	marker	tibia, ventricular zone, epithelium of nasopharynx
SF3B2	292	ubiquitous	marker	ventricular zone, left testis, right testis
IKZF1	225	broad	marker	leukocyte, monocyte, mononuclear cell
DCPH1	285	ubiquitous	marker	cartilage tissue, endometrium, palpebral conjunctiva
WSB1	303	ubiquitous	marker	corpus callosum, mucosa of stomach, lower lobe of lung
ZBTB2	231	ubiquitous	marker	secondary oocyte, oocyte, epithelial cell of pancreas
MTHFD1L	236	ubiquitous	yes	right coronary artery, stromal cell of endometrium, left coronary artery
RMND1	273	ubiquitous	marker	primordial germ cell in gonad, ganglionic eminence, calcaneal tendon
CCDC170	182	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
FAM27E5	35		yes	ventricular zone, right lobe of liver, cortical plate
ESR1	216	broad	marker	oviduct epithelium, cervix epithelium, mammalian vulva
AKAP12	287	ubiquitous	marker	pons, lateral nuclear group of thalamus, dorsal root ganglion
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 28.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EGFR	18,421
KRAS	14,509
ESR1	12,382
NRAS	7,598
ABL1	6,937
JAK2	6,197
KIT	6,087
LYN	5,710
PDGFRA	5,186
SF3B1	4,582

Intra-cohort edges

A	B	Sources
ABL1	BCR	string_interaction
ABL1	EGFR	intact
ABL1	IKZF1	string_interaction
AKAP12	DCPH1	string_interaction
AKAP12	EGFR	intact
AKAP12	NRAS	intact
AKAP12	ZBTB2	string_interaction
BCR	KIT	biogrid_interaction
CCDC170	DCPH1	string_interaction
CCDC170	ESR1	string_interaction
CCDC170	RMND1	string_interaction
CCDC170	ZBTB2	string_interaction
DCPH1	ESR1	string_interaction
DCPH1	MTHFD1L	string_interaction
DCPH1	RMND1	string_interaction
DCPH1	ZBTB2	string_interaction
EGFR	JAK2	biogrid_interaction
EGFR	LYN	intact
EGFR	NRAS	string_interaction
EGFR	PDGFRA	intact
EGFR	RET	intact
ESR1	MTHFD1L	intact
KRAS	NRAS	intact
MTHFD1L	RMND1	string_interaction
MTHFD1L	ZBTB2	string_interaction
NRAS	SETBP1	string_interaction
RMND1	ZBTB2	string_interaction
SF3B1	SF3B2	string_interaction

Structural data

PDB: 17 · AlphaFold-only: 7 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
ESR1	P03372	478
EGFR	P00533	388
JAK2	O60674	164
ABL1	P00519	85
SF3B1	O75533	74
KIT	P10721	52
SF3B2	Q13435	50
BCL2L11	O43521	45
NRAS	P01111	35
RET	P07949	34
ABCB1	P08183	24
PDGFRA	P16234	15
IKZF1	Q13422	10
LYN	P07948	6
BCR	P11274	5
DCPH1	Q9H993	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MTHFD1L	Q6UB35	87.45
WSB1	Q9Y6I7	84.61
CCDC170	Q8IYT3	82.06
RMND1	Q9NWS8	70.28
ZBTB2	Q8N680	57.51
SETBP1	Q9Y6X0	43.30
AKAP12	Q02952	40.98

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 320. Enrichment computed across 25 evidence-associated genes (19 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 19 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	136.6×	6e-08	JAK2, KIT, KRAS, LYN, NRAS
Erythropoietin activates RAS	4	160.3×	1e-06	JAK2, KRAS, LYN, NRAS
Signaling by SCF-KIT	5	65.3×	1e-06	JAK2, KIT, KRAS, LYN, NRAS
RAF/MAP kinase cascade	7	22.5×	1e-06	EGFR, JAK2, KIT, KRAS, NRAS, PDGFRA, RET
EGFR Transactivation by Gastrin	3	180.3×	2e-05	EGFR, KRAS, NRAS
Signaling by KIT in disease	3	180.3×	2e-05	JAK2, KIT, LYN
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	3	138.7×	4e-05	KRAS, NRAS, PDGFRA
Signaling by PDGFRA extracellular domain mutants	3	138.7×	4e-05	KRAS, NRAS, PDGFRA
GRB2 events in EGFR signaling	3	120.2×	6e-05	EGFR, KRAS, NRAS
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	3	120.2×	6e-05	EGFR, ESR1, KIT
SHC1 events in EGFR signaling	3	112.7×	6e-05	EGFR, KRAS, NRAS
Constitutive Signaling by EGFRvIII	3	112.7×	6e-05	EGFR, KRAS, NRAS
Signaling by ERBB2 ECD mutants	3	106.1×	6e-05	EGFR, KRAS, NRAS
GRB2 events in ERBB2 signaling	3	100.2×	7e-05	EGFR, KRAS, NRAS
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	3	90.2×	8e-05	EGFR, KRAS, NRAS
Signaling by CSF3 (G-CSF)	3	90.2×	8e-05	JAK2, KRAS, LYN
Signaling by BRAF and RAF1 fusions	4	35.9×	8e-05	JAK2, KRAS, NRAS, BCL2L11
CD209 (DC-SIGN) signaling	3	82.0×	1e-04	KRAS, LYN, NRAS
Signaling by RAS GAP mutants	2	400.7×	1e-04	KRAS, NRAS
Signaling by RAS GTPase mutants	2	400.7×	1e-04	KRAS, NRAS
SHC1 events in ERBB2 signaling	3	75.1×	1e-04	EGFR, KRAS, NRAS
Signaling by ERBB2 TMD/JMD mutants	3	75.1×	1e-04	EGFR, KRAS, NRAS
Signaling by ERBB2 KD Mutants	3	66.8×	2e-04	EGFR, KRAS, NRAS
Constitutive Signaling by Aberrant PI3K in Cancer	4	26.7×	2e-04	EGFR, ESR1, KIT, PDGFRA
G1 Phase	3	62.2×	2e-04	ABL1, JAK2, LYN
Downstream signal transduction	3	60.1×	2e-04	KRAS, NRAS, PDGFRA
Diseases of signal transduction by growth factor receptors and second messengers	5	14.9×	2e-04	BCR, JAK2, KIT, LYN, BCL2L11
FCERI mediated MAPK activation	3	54.6×	2e-04	KRAS, LYN, NRAS
FLT3 Signaling	3	54.6×	2e-04	KRAS, NRAS, BCL2L11
RAF activation	3	53.0×	2e-04	JAK2, KRAS, NRAS

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 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 fibroblast proliferation	4	49.3×	4e-04	ABL1, EGFR, ESR1, PDGFRA
erythrocyte differentiation	4	44.6×	4e-04	IKZF1, JAK2, KIT, LYN
positive regulation of cell migration	6	15.4×	4e-04	EGFR, JAK2, KIT, LYN, PDGFRA, RET
positive regulation of MAPK cascade	5	16.8×	0.001	EGFR, JAK2, KIT, LYN, RET
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	16.3×	0.001	EGFR, JAK2, KIT, PDGFRA, RET
positive regulation of mast cell proliferation	2	280.9×	0.002	KIT, LYN
interleukin-5-mediated signaling pathway	2	234.1×	0.002	JAK2, LYN
erythropoietin-mediated signaling pathway	2	234.1×	0.002	JAK2, KIT
cellular response to estradiol stimulus	3	51.4×	0.002	EGFR, ESR1, ABCB1
protein autophosphorylation	4	24.2×	0.002	JAK2, KIT, LYN, PDGFRA
signal transduction	8	5.3×	0.004	BCR, EGFR, ESR1, AKAP12, JAK2, KIT, LYN, RET
growth hormone receptor signaling pathway via JAK-STAT	2	127.7×	0.005	JAK2, LYN
myoblast proliferation	2	117.0×	0.006	ABL1, KRAS
hematopoietic progenitor cell differentiation	3	29.7×	0.006	KIT, LYN, PDGFRA
positive regulation of ERK1 and ERK2 cascade	4	14.2×	0.007	ABL1, EGFR, AKAP12, PDGFRA
actin cytoskeleton organization	4	13.2×	0.008	ABL1, BCR, KIT, KRAS
negative regulation of cell-cell adhesion	2	82.6×	0.009	ABL1, JAK2
modulation of chemical synaptic transmission	3	22.9×	0.010	BCR, AKAP12, JAK2
cell surface receptor protein tyrosine kinase signaling pathway	3	21.7×	0.011	LYN, PDGFRA, RET
positive regulation of phosphorylation	2	70.2×	0.011	EGFR, LYN
positive regulation of tyrosine phosphorylation of STAT protein	2	61.1×	0.012	JAK2, KIT
response to cadmium ion	2	61.1×	0.012	ABCB1, KIT
Fc-gamma receptor signaling pathway involved in phagocytosis	2	58.5×	0.012	ABL1, LYN
positive regulation of glial cell proliferation	2	58.5×	0.012	KRAS, LYN
male gonad development	3	19.5×	0.012	ESR1, KIT, BCL2L11
MAPK cascade	3	19.1×	0.012	KRAS, NRAS, RET
negative regulation of cellular extravasation	1	702.2×	0.014	BCR
negative regulation of myeloid leukocyte differentiation	1	702.2×	0.014	LYN
nuclear receptor-mediated mineralocorticoid signaling pathway	1	702.2×	0.014	JAK2
symbiont-induced defense-related programmed cell death	1	702.2×	0.014	JAK2

Therapeutics

Drugs indicated for this disease

4 approved, 18 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Busulfan	Approved (phase 4)
Dasatinib Anhydrous	Approved (phase 4)
Hydroxyurea	Approved (phase 4)
INTERFERON ALFA-2B	Approved (phase 4)
Asciminib	Phase 3 (in late-stage trials)
Bosutinib	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Flumatinib	Phase 3 (in late-stage trials)
Imatinib	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Nilotinib	Phase 3 (in late-stage trials)
Olverembatinib	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2A	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Ponatinib	Phase 3 (in late-stage trials)
Radotinib	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aldesleukin, Aspirin, Bevacizumab, Bortezomib, Clofarabine, Decitabine, Filgrastim, Idarubicin, Ketoconazole, Lonafarnib, Maraviroc, Melphalan, Motixafortide, Oblimersen Sodium, Omacetaxine Mepesuccinate, Oprelvekin, Panobinostat, Pioglitazone, Rituximab, Ruxolitinib, Sorafenib, Tacrolimus Anhydrous, Thiotepa, Valproic Acid, Venetoclax.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 13 · Phased (≥1): 16 · Undrugged: 9

Druggability breadth: 19 of 25 evidence-associated genes (76%) 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
ABL1	PONATINIB
EGFR	LEVODOPA
ABCB1	PROGESTERONE
JAK2	FEDRATINIB
KIT	PONATINIB
LYN	PONATINIB
PDGFRA	PONATINIB
RET	PONATINIB
BCR	PONATINIB
IKZF1	POMALIDOMIDE
ESR1	CANDESARTAN CILEXETIL
KRAS	VEMURAFENIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
EGFR	175	4
ESR1	162	4
RET	135	4
ABL1	122	4
ABCB1	119	4
JAK2	100	4
KIT	99	4
LYN	83	4
PDGFRA	77	4
BCR	64	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	ABL1, BCR, EGFR, JAK2, KIT, LYN
AFATINIB	4	ABL1, EGFR, LYN, RET
FEDRATINIB	4	ABL1, BCR, EGFR, JAK2, KIT, LYN
TIVOZANIB	4	ABL1, BCR, KIT, LYN, PDGFRA, RET
LENVATINIB	4	ABL1, BCR, ESR1, KIT, PDGFRA, RET
AXITINIB	4	ABL1, BCR, EGFR, JAK2, KIT, PDGFRA
SORAFENIB	4	ABL1, EGFR, KIT, LYN, PDGFRA, RET
DASATINIB ANHYDROUS	4	ABL1, BCR, EGFR, KIT, LYN, RET
IMATINIB MESYLATE	4	ABL1, BCR, KIT, PDGFRA
RUXOLITINIB	4	ABL1, JAK2, KIT, RET
NERATINIB	4	ABL1, EGFR, LYN
INFIGRATINIB PHOSPHATE	4	ABL1, JAK2, KIT, LYN, PDGFRA, RET
INFIGRATINIB	4	ABL1, BCR, JAK2, KIT, LYN, PDGFRA
IBRUTINIB	4	ABL1, BCR, EGFR, LYN, RET
REGORAFENIB	4	ABL1, BCR, KIT, PDGFRA, RET
ENTRECTINIB	4	ABL1, JAK2, KIT, LYN, RET
DABRAFENIB	4	ABL1, JAK2, KRAS, LYN
TOFACITINIB CITRATE	4	ABL1, JAK2, RET
AFATINIB DIMALEATE	4	ABL1, EGFR
CABOZANTINIB	4	ABL1, BCR, EGFR, KIT, LYN, RET
TOFACITINIB	4	ABL1, JAK2, RET
CERITINIB	4	ABCB1, ABL1, EGFR, JAK2, KIT, LYN
VANDETANIB	4	ABL1, BCR, EGFR, KIT, LYN, PDGFRA
NILOTINIB	4	ABL1, BCR, KIT, LYN, PDGFRA, RET
BOSUTINIB	4	ABL1, BCR, EGFR, JAK2, KIT, LYN
FILGOTINIB	4	ABL1, JAK2
TOVORAFENIB	4	ABL1, BCR
BRIGATINIB	4	ABL1, EGFR, JAK2, KIT, LYN, RET
ASCIMINIB	4	ABL1, BCR
PAZOPANIB	4	ABL1, JAK2, KIT, LYN, PDGFRA, RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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

Symbol	Assays	Type breakdown
EGFR	6,531	Binding:6211, Functional:173, ADMET:138, Toxicity:9
ABL1	3,282	Binding:3254, ADMET:16, Functional:10, Toxicity:2
ABCB1	3,063	Binding:2135, Functional:746, ADMET:182
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
KIT	2,305	Binding:2242, ADMET:32, Functional:22, Toxicity:9
JAK2	2,018	Binding:1911, Functional:51, ADMET:48, Unclassified:4, Toxicity:4
RET	1,586	Binding:1573, Functional:10, ADMET:3
PDGFRA	1,172	Binding:1160, Functional:8, ADMET:4
KRAS	861	Binding:829, Functional:32
LYN	820	Binding:814, ADMET:4, Functional:2
BCR	486	Binding:478, Functional:6, Toxicity:2
IKZF1	106	Binding:105, Functional:1
BCL2L11	38	Binding:36, Functional:2
SF3B1	22	Binding:22
SF3B2	20	Binding:20
NRAS	18	Binding:18
MTHFD1L	4	Binding:4
ZBTB2	3	Binding:3
AKAP12	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ABL1	2.7.10.2	non-specific protein-tyrosine kinase
EGFR	2.7.10.1	receptor protein-tyrosine kinase
ABCB1	7.6.2.2, 7.6.2.3	ABC-type xenobiotic transporter, ABC-type glutathione-S-conjugate transporter
JAK2	2.7.10.2	non-specific protein-tyrosine kinase
KIT	2.7.10.1	receptor protein-tyrosine kinase
LYN	2.7.10.2	non-specific protein-tyrosine kinase
PDGFRA	2.7.10.1	receptor protein-tyrosine kinase
RET	2.7.10.1	receptor protein-tyrosine kinase
MTHFD1L	6.3.4.3	formate-tetrahydrofolate ligase
KRAS	3.6.5.2	small monomeric GTPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ABL1	3,282
EGFR	6,531
ABCB1	3,063
JAK2	2,018
KIT	2,305
LYN	820
PDGFRA	1,172
RET	1,586
BCR	486
IKZF1	106
ESR1	2,435
KRAS	861

Pharmacogenomics

Cohort genes with a PharmGKB record: 24; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

25 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)
AFATINIB	4	ABL1, EGFR, LYN, RET
FEDRATINIB	4	ABL1, BCR, EGFR, JAK2, KIT, LYN
TIVOZANIB	4	ABL1, BCR, KIT, LYN, PDGFRA, RET
LENVATINIB	4	ABL1, BCR, ESR1, KIT, PDGFRA, RET
AXITINIB	4	ABL1, BCR, EGFR, JAK2, KIT, PDGFRA
SORAFENIB	4	ABL1, EGFR, KIT, LYN, PDGFRA, RET
IMATINIB MESYLATE	4	ABL1, BCR, KIT, PDGFRA
RUXOLITINIB	4	ABL1, JAK2, KIT, RET
NERATINIB	4	ABL1, EGFR, LYN
INFIGRATINIB PHOSPHATE	4	ABL1, JAK2, KIT, LYN, PDGFRA, RET
INFIGRATINIB	4	ABL1, BCR, JAK2, KIT, LYN, PDGFRA
IBRUTINIB	4	ABL1, BCR, EGFR, LYN, RET
REGORAFENIB	4	ABL1, BCR, KIT, PDGFRA, RET
ENTRECTINIB	4	ABL1, JAK2, KIT, LYN, RET
DABRAFENIB	4	ABL1, JAK2, KRAS, LYN
TOFACITINIB CITRATE	4	ABL1, JAK2, RET
AFATINIB DIMALEATE	4	ABL1, EGFR
CABOZANTINIB	4	ABL1, BCR, EGFR, KIT, LYN, RET
TOFACITINIB	4	ABL1, JAK2, RET
CERITINIB	4	ABCB1, ABL1, EGFR, JAK2, KIT, LYN
VANDETANIB	4	ABL1, BCR, EGFR, KIT, LYN, PDGFRA
FILGOTINIB	4	ABL1, JAK2
TOVORAFENIB	4	ABL1, BCR
BRIGATINIB	4	ABL1, EGFR, JAK2, KIT, LYN, RET
PAZOPANIB	4	ABL1, JAK2, KIT, LYN, PDGFRA, RET

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	ABL1, EGFR, ABCB1, JAK2, KIT, LYN, PDGFRA, RET, BCR, IKZF1 (+2 more)
B	Phased (≥1) drug, not yet approved	4	BCL2L11, SF3B1, SF3B2, NRAS
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	MTHFD1L
E	Difficult family or no structure, no drug	8	SETBP1, DCPH1, WSB1, ZBTB2, RMND1, CCDC170, FAM27E5, AKAP12

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CCDC170	0	ESR1
SETBP1	0	—
DCPH1	0	—
WSB1	0	—
ZBTB2	3	—
MTHFD1L	4	—
RMND1	0	—
FAM27E5	0	—
AKAP12	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 652.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	217
Not specified	173
PHASE1	124
PHASE1/PHASE2	61
PHASE3	41
PHASE4	23
PHASE2/PHASE3	7
EARLY_PHASE1	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04877522	PHASE4	RECRUITING	Asciminib Roll-over Study
NCT00081926	PHASE4	COMPLETED	Gleevec Trial in Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
NCT00171899	PHASE4	COMPLETED	Study Comparing Standard Dose and High-dose Imatinib Mesylate in Patients With Chronic Phase Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML)
NCT00390897	PHASE4	COMPLETED	Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia
NCT00461929	PHASE4	TERMINATED	Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib
NCT00786812	PHASE4	COMPLETED	Study of Treatment With Nilotinib in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase
NCT00845221	PHASE4	COMPLETED	Glivec in Pediatric Chronic Myeloid Leukemia (CML)
NCT00980018	PHASE4	COMPLETED	An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
NCT01131325	PHASE4	TERMINATED	Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
NCT01206088	PHASE4	COMPLETED	Tasigna in Glivec-resistant or Intolerant Patients in CML
NCT01243489	PHASE4	COMPLETED	Compliance: Role Emerges for Success in Chronic Myelogenous Leukaemia (CML): Evaluation aND Optimisation
NCT01368523	PHASE4	COMPLETED	Study of Oral AMN107 (Nilotinib) in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase Previously Enrolled to CAMN107A2109 Trial
NCT01578213	PHASE4	COMPLETED	Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients
NCT01605981	PHASE4	WITHDRAWN	Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.
NCT01735955	PHASE4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01901666	PHASE4	UNKNOWN	Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
NCT02086487	PHASE4	TERMINATED	Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy
NCT02204722	PHASE4	TERMINATED	A Study to Evaluate Efficacy and Safety of Glinib in Newly Diagnosed CML Patients
NCT02317159	PHASE4	UNKNOWN	Efficacy and Safety of Imatinib Mesylate as First-line Treatment for the Patients With Chronic Phase of Chronic Myeloid Leukemia
NCT02546674	PHASE4	COMPLETED	Study Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline.
NCT03216070	PHASE4	UNKNOWN	Low-dose Dasatinib as First-line Treatment for Chronic Myeloid Leukemia
NCT04155411	PHASE4	UNKNOWN	Dose Reduced Dasatinib (70 mg Daily) as First-line Treatment for Newly Diagnosed CML-CP
NCT07105319	PHASE4	COMPLETED	Ropeginterferon for Treatment Free Remission
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT05753384	PHASE3	ACTIVE_NOT_RECRUITING	Discontinuation of TyrosIne Kinase Inhibitors (TKI) in Chronic Myeloid Leukemia (CML) and Impact on the Immune System
NCT06423911	PHASE3	RECRUITING	Study of Olverembatinib (HQP1351) in Patients With CP-CML
NCT07489755	PHASE3	NOT_YET_RECRUITING	TGRX-678 Chinese Phase III in Chronic Myelogenous Leukemia (CML) Patients
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00219739	PHASE3	COMPLETED	STI571 ProspectIve RandomIzed Trial: SPIRIT
NCT00327262	PHASE3	UNKNOWN	Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
NCT00333840	PHASE3	COMPLETED	Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
NCT00349518	PHASE2/PHASE3	WITHDRAWN	Study of Dasatinib in Imatinib Resistant or Intolerant Subjects With Chronic or Advanced Phase CML or Philadelphia Chromosome Positive ALL
NCT00354120	PHASE2/PHASE3	COMPLETED	Thymoglobuline Versus Alemtuzumab in Patients Undergoing Allogeneic Transplant
NCT00412360	PHASE3	COMPLETED	Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00469729	PHASE2/PHASE3	COMPLETED	Efficacy and Safety Study of StemEx®, to Treat Subjects With High Risk Hematologic Malignancies, Following Myeloablative Therapy
NCT00481247	PHASE3	COMPLETED	A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
NCT00514488	PHASE3	COMPLETED	Imatinib Standard Dose (400 mg/Day) Versus Imatinib High Dose (800 mg/Day)
NCT00574873	PHASE3	COMPLETED	Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
NCT00760877	PHASE3	COMPLETED	Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IMATINIB	4	71
NILOTINIB	4	37
DASATINIB ANHYDROUS	4	34
BOSUTINIB	4	17
PONATINIB	4	17
ASCIMINIB	4	12
PLERIXAFOR	4	9
CLOFARABINE	4	7
VORINOSTAT	4	7
OMACETAXINE MEPESUCCINATE	4	6
FLUDARABINE PHOSPHATE	4	5
2-MERCAPTOETHANESULFONIC ACID	4	4
DECITABINE	4	4
THIOTEPA	4	4
ALEMTUZUMAB	4	3
IPILIMUMAB	4	3
PALIFERMIN	4	3
PENTOSTATIN	4	3
BASILIXIMAB	4	2
BELINOSTAT	4	2
BLINATUMOMAB	4	2
IDARUBICIN	4	2
MELPHALAN	4	2
APREPITANT	4	1
ARMODAFINIL	4	1
ARTESUNATE	4	1
ATORVASTATIN CALCIUM	4	1
BECLOMETHASONE DIPROPIONATE	4	1
BENDAMUSTINE	4	1
BENDAMUSTINE HYDROCHLORIDE	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 336 predictive associations from 486 curated evidence items; also 7 diagnostic, 2 oncogenic, 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
BCR::ABL1 Fusion	Asciminib	Sensitivity/Response	CIViC A	EID11223 +1
BCR::ABL1 Fusion	Imatinib	Sensitivity/Response	CIViC A	EID260 +1
ABL1 T315I	Asciminib	Sensitivity/Response	CIViC A	EID11225
ABL1 T315I	Ponatinib	Sensitivity/Response	CIViC A	EID11226
BCR::ABL1 Fusion	Bosutinib	Sensitivity/Response	CIViC A	EID11224
BCR::ABL1 Fusion	Nilotinib + Dasatinib	Sensitivity/Response	CIViC A	EID261
BCR::ABL1 Fusion AND ABL1 TKD Mutation	Bosutinib	Sensitivity/Response	CIViC A	EID11289
BCR::ABL1 Fusion AND ABL1 TKD Mutation	Dasatinib	Sensitivity/Response	CIViC A	EID11342
BCR::ABL1 Fusion AND ABL1 T315I	Ponatinib	Sensitivity/Response	CIViC B	EID1390 +2
BCR::ABL1 Fusion AND ABL1 M351T	Bosutinib	Sensitivity/Response	CIViC B	EID4393 +1
BCR::ABL1 Fusion AND ABL1 T315I	Omacetaxine Mepesuccinate	Sensitivity/Response	CIViC B	EID6197 +1
ABL1 I418S	Dasatinib	Sensitivity/Response	CIViC B	EID4715
BCL2L11 Deletion Polymorphism	Imatinib	Sensitivity/Response	CIViC B	EID9701
BCR::ABL1 Fusion AND ABL1 F317L	Dasatinib	Resistance	CIViC B	EID6309 +6
BCR::ABL1 Fusion AND ABL1 T315I	Dasatinib	Resistance	CIViC B	EID4365 +5
BCR::ABL1 Fusion AND ABL1 T315I	Imatinib	Resistance	CIViC B	EID234 +4
BCR::ABL1 Fusion AND ABL1 Y253H	Dasatinib	Resistance	CIViC B	EID4335 +3
BCR::ABL1 Fusion AND ABL1 E255V	Dasatinib	Resistance	CIViC B	EID4447 +2
BCR::ABL1 Fusion AND ABL1 E355G	Dasatinib	Resistance	CIViC B	EID4403 +2
BCR::ABL1 Fusion AND ABL1 F359V	Dasatinib	Resistance	CIViC B	EID3819 +2
BCR::ABL1 Fusion AND ABL1 M244V	Dasatinib	Resistance	CIViC B	EID4302 +2
BCR::ABL1 Fusion AND ABL1 M351T	Dasatinib	Resistance	CIViC B	EID4396 +2
ABL1 Non-P-Loop Mutation	Bosutinib	Resistance	CIViC B	EID6337 +1
ABL1 P-Loop Mutation	Bosutinib	Resistance	CIViC B	EID6336 +1
ABL1 TKD Mutation	Bosutinib	Resistance	CIViC B	EID6335 +1
BCR::ABL1 Fusion AND ABL1 E255K	Dasatinib	Resistance	CIViC B	EID4350 +1
BCR::ABL1 Fusion AND ABL1 E459K	Dasatinib	Resistance	CIViC B	EID6310 +1
BCR::ABL1 Fusion AND ABL1 F359I	Dasatinib	Resistance	CIViC B	EID4532 +1
BCR::ABL1 Fusion AND ABL1 F486S	Dasatinib	Resistance	CIViC B	EID4571 +1
BCR::ABL1 Fusion AND ABL1 G250E	Dasatinib	Resistance	CIViC B	EID4316 +1

+306 more predictive associations (showing top 30 by evidence level).