atypical chronic myeloid leukemia, BCR-ABL1 negative

Summary

atypical chronic myeloid leukemia, BCR-ABL1 negative (MONDO:0004653) is a cancer with 7 cohort genes (6 CIViC-evidence somatic drivers; 6 ClinVar predisposition records) and 33 clinical trials. Molecularly, NTRK2 R458G confers sensitivity to Larotrectinib + Entrectinib in Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative (CIViC Level C). Top therapeutic interventions include fludarabine phosphate, dacomitinib anhydrous, and alemtuzumab.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 7
• ClinVar variants: 6
• Clinical trials: 33
• Precision-medicine evidence (CIViC): 1 subtype–drug association

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	<1 / 1 000 000		Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	atypical chronic myeloid leukemia, BCR-ABL1 negative
Mondo ID	MONDO:0004653
Orphanet	98824
DOID	DOID:0060597, DOID:8747
ICD-11	331838766
NCIT	C3519
SNOMED CT	277589003
UMLS	C1292772
MedGen	266233
GARD	0019583
MedDRA	10054651
Is cancer (heuristic)	yes

Also known as: aCML · atypical chronic myeloid leukaemia · atypical chronic myeloid leukemia · atypical chronic myeloid leukemia, BCR-ABL1 Negative · atypical CML · subacute granulocytic leukaemia · subacute granulocytic leukemia · subacute myelogenous leukaemia · subacute myelogenous leukemia · subacute myeloid leukaemia · subacute myeloid leukemia

Data availability: 6 ClinVar variants · 3 cell lines.

Disease family

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 › atypical chronic myeloid leukemia, BCR-ABL1 negative

Related subtypes (3): chronic myeloid leukemia, acute myeloid leukemia, Philadelphia-positive myelogenous leukemia

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

6 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 2 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2504109	NM_015338.6(ASXL1):c.1892_1938del (p.His631fs)	ASXL1	Pathogenic	no assertion criteria provided
2504111	NM_001195427.2(SRSF2):c.284C>T (p.Pro95Leu)	MFSD11	Pathogenic	no assertion criteria provided
590265	t(13;17)(q12.2;q11.2)	FLT3	Likely pathogenic	no assertion criteria provided
2504110	NM_001754.5(RUNX1):c.1256_1262dup (p.Glu422fs)	RUNX1	Likely pathogenic	reviewed by expert panel
2416868	NM_001127208.3(TET2):c.5618T>C (p.Ile1873Thr)	TET2	Uncertain significance	criteria provided, single submitter
2504112	NM_001127208.3(TET2):c.3782G>A (p.Arg1261His)	TET2	Uncertain significance	criteria provided, single submitter

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
SETBP1	Act	ACC	CIViC #10024
CSF3R	LoF	AML,BLADDER,HNSC	CIViC #1239
RUNX1	LoF	ACYC,ALL,AML,BRCA,GBM	CIViC #43
ASXL1	LoF	AML,BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,ESCA,HGGNOS,HNSC,MBL,PAST,PRAD,STOMACH	CIViC #68
TET2	LoF	AML,MDS,MLYM,NHL,PCM,RCC,SOFT_TISSUE	CIViC #55
FLT3	Act	ALL,AML	CIViC #24

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SETBP1	Orphanet:436151	Intellectual disability-expressive aphasia-facial dysmorphism syndrome
SETBP1	Orphanet:798	Schinzel-Giedion syndrome
CSF3R	Orphanet:279943	Hereditary neutrophilia
CSF3R	Orphanet:420702	Autosomal recessive severe congenital neutropenia due to CSF3R deficiency
CSF3R	Orphanet:86829	Chronic neutrophilic leukemia
CSF3R	Orphanet:98824	Atypical chronic myeloid leukemia
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
ASXL1	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
ASXL1	Orphanet:97297	Bohring-Opitz syndrome
ASXL1	Orphanet:98823	Chronic myelomonocytic leukemia
ASXL1	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
ASXL1	Orphanet:98850	Aggressive systemic mastocytosis
TET2	Orphanet:100019	Myelodysplastic neoplasm with increased blasts type 1
TET2	Orphanet:100020	Myelodysplastic neoplasm with increased blasts type 2
TET2	Orphanet:3318	Essential thrombocythemia
TET2	Orphanet:664729	EBV-induced lymphoproliferative disease due to TET2 deficiency
TET2	Orphanet:75564	Acquired idiopathic sideroblastic anemia
TET2	Orphanet:824	Primary myelofibrosis
TET2	Orphanet:86845	Acute myeloid leukaemia with myelodysplasia-related features
TET2	Orphanet:98826	Myelodysplastic neoplasm with low blasts
TET2	Orphanet:98849	Systemic mastocytosis with associated hematologic neoplasm
TET2	Orphanet:98850	Aggressive systemic mastocytosis
FLT3	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
FLT3	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
FLT3	Orphanet:589534	Mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2)
FLT3	Orphanet:589595	Mixed phenotype acute leukemia with t(v;11q23.3)
FLT3	Orphanet:98829	Acute myeloid leukemia with abnormal bone marrow eosinophils inv(16)(p13q22) or t(16;16)(p13;q22)
FLT3	Orphanet:98832	Acute myeloid leukemia with minimal differentiation
FLT3	Orphanet:98833	Acute myeloblastic leukemia without maturation
FLT3	Orphanet:98834	Acute myeloblastic leukemia with maturation
FLT3	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia

Cohort genes → proteins

7 cohort genes, 7 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	2
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SETBP1	HGNC:15573	ENSG00000152217	Q9Y6X0	SET-binding protein	civic_evidence
CSF3R	HGNC:2439	ENSG00000119535	Q99062	Granulocyte colony-stimulating factor receptor	civic_evidence
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	clinvar
ASXL1	HGNC:18318	ENSG00000171456	Q8IXJ9	Polycomb group protein ASXL1	clinvar
MFSD11	HGNC:25458	ENSG00000092931	O43934	UNC93-like protein MFSD11	clinvar
TET2	HGNC:25941	ENSG00000168769	Q6N021	Methylcytosine dioxygenase TET2	clinvar
FLT3	HGNC:3765	ENSG00000122025	P36888	Receptor-type tyrosine-protein kinase FLT3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF3R	Granulocyte colony-stimulating factor receptor	Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation.
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
ASXL1	Polycomb group protein ASXL1	Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG).
TET2	Methylcytosine dioxygenase TET2	Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation.
FLT3	Receptor-type tyrosine-protein kinase FLT3	Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells.

Protein-family classification

Druggable: 3 · Difficult: 1 · Unknown: 3 · 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
Ion channel	1	15.9×	0.306
Antibody/Immunoglobulin	1	4.2×	0.378
Kinase	1	4.0×	0.378
Transcription factor	1	1.2×	0.744
Other/Unknown	3	0.8×	0.858

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SETBP1	Other/Unknown	no		AT_hook_DNA-bd_motif
CSF3R	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
ASXL1	Other/Unknown	no		Asxl_HARE-HTH, ASX/ASX-like, ASX-like_PHD
MFSD11	Ion channel	yes		Ion_channel_UNC-93, MFS_trans_sf, UNC-93-like_regulator
TET2	Other/Unknown	no		2OGFeDO_JBP1/TET_oxygenase_dom, TET1/2/3, TET_oxygenase
FLT3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

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
buccal mucosa cell	2
adrenal tissue	2
caput epididymis	1
ventricular zone	1
blood	1
granulocyte	1
monocyte	1
epithelium of bronchus	1
mucosa of paranasal sinus	1
olfactory segment of nasal mucosa	1
sperm	1
sural nerve	1
primordial germ cell in gonad	1
amniotic fluid	1
epithelium of nasopharynx	1
palpebral conjunctiva	1
cerebellar cortex	1
cerebellar hemisphere	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SETBP1	280	ubiquitous	marker	ventricular zone, buccal mucosa cell, caput epididymis
CSF3R	192	broad	marker	granulocyte, monocyte, blood
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
ASXL1	294	ubiquitous	marker	sural nerve, sperm, adrenal tissue
MFSD11	244	ubiquitous	marker	buccal mucosa cell, adrenal tissue, primordial germ cell in gonad
TET2	249	ubiquitous	marker	palpebral conjunctiva, amniotic fluid, epithelium of nasopharynx
FLT3	166	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 9.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RUNX1	4,994
FLT3	3,570
CSF3R	3,315
TET2	2,965
ASXL1	2,816
SETBP1	2,077
MFSD11	1,076

Intra-cohort edges

A	B	Sources
ASXL1	FLT3	string_interaction
ASXL1	RUNX1	string_interaction
ASXL1	SETBP1	string_interaction
ASXL1	TET2	string_interaction
CSF3R	SETBP1	string_interaction
FLT3	RUNX1	string_interaction
FLT3	TET2	string_interaction
RUNX1	SETBP1	string_interaction
SETBP1	TET2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FLT3	P36888	11
TET2	Q6N021	6
RUNX1	Q01196	5
ASXL1	Q8IXJ9	4
CSF3R	Q99062	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MFSD11	O43934	87.72
SETBP1	Q9Y6X0	43.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 81. Enrichment computed across 7 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FLT3 mutants bind TKIs	1	2284.0×	0.002	FLT3
KW2449-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
semaxanib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
crenolanib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
gilteritinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
lestaurtinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
midostaurin-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
pexidartinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
ponatinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
quizartinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
sorafenib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
sunitinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
tandutinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
linifanib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
tamatinib-resistant FLT3 mutants	1	2284.0×	0.002	FLT3
Transcriptional regulation of granulopoiesis	2	50.2×	0.003	RUNX1, CSF3R
RUNX3 regulates RUNX1-mediated transcription	1	761.3×	0.006	RUNX1
TET1,2,3 and TDG demethylate DNA	1	571.0×	0.008	TET2
RUNX1 regulates expression of components of tight junctions	1	456.8×	0.008	RUNX1
RUNX1 regulates transcription of genes involved in interleukin signaling	1	456.8×	0.008	RUNX1
RUNX2 regulates genes involved in differentiation of myeloid cells	1	456.8×	0.008	RUNX1
RUNX1 regulates estrogen receptor mediated transcription	1	380.7×	0.009	RUNX1
RUNX1 regulates transcription of genes involved in BCR signaling	1	380.7×	0.009	RUNX1
RUNX1 regulates transcription of genes involved in WNT signaling	1	380.7×	0.009	RUNX1
STAT5 Activation	1	326.3×	0.009	FLT3
FLT3 signaling through SRC family kinases	1	326.3×	0.009	FLT3
FLT3 signaling by CBL mutants	1	326.3×	0.009	FLT3
RUNX1 regulates transcription of genes involved in differentiation of myeloid cells	1	285.5×	0.010	RUNX1
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	1	228.4×	0.011	RUNX1
RUNX1 regulates transcription of genes involved in differentiation of keratinocytes	1	228.4×	0.011	RUNX1

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
hemopoiesis	3	114.6×	1e-04	RUNX1, ASXL1, FLT3
myeloid cell differentiation	2	185.2×	0.002	RUNX1, TET2
regulation of connective tissue replacement	1	2407.4×	0.009	RUNX1
regulation of kidney size	1	1203.7×	0.009	ASXL1
leukocyte homeostasis	1	802.5×	0.009	FLT3
myeloid leukocyte differentiation	1	802.5×	0.009	RUNX1
regulation of plasminogen activation	1	802.5×	0.009	RUNX1
pro-B cell differentiation	1	601.9×	0.009	FLT3
negative regulation of CD4-positive, alpha-beta T cell differentiation	1	601.9×	0.009	RUNX1
cardiac muscle tissue regeneration	1	601.9×	0.009	RUNX1
positive regulation of extracellular matrix organization	1	601.9×	0.009	RUNX1
leukocyte differentiation	1	481.5×	0.009	TET2
positive regulation of CD8-positive, alpha-beta T cell differentiation	1	481.5×	0.009	RUNX1
regulation of myeloid cell differentiation	1	481.5×	0.009	CSF3R
positive regulation of retinoic acid receptor signaling pathway	1	481.5×	0.009	ASXL1
regulation of cardiac muscle cell proliferation	1	481.5×	0.009	RUNX1
cytokine-mediated signaling pathway	2	37.3×	0.009	CSF3R, FLT3
positive regulation of granulocyte differentiation	1	401.2×	0.009	RUNX1
negative regulation of peroxisome proliferator activated receptor signaling pathway	1	401.2×	0.009	ASXL1
myeloid progenitor cell differentiation	1	343.9×	0.010	FLT3
lymphocyte proliferation	1	343.9×	0.010	FLT3
negative regulation of granulocyte differentiation	1	300.9×	0.010	RUNX1
lung saccule development	1	300.9×	0.010	ASXL1
common myeloid progenitor cell proliferation	1	267.5×	0.011	FLT3
bone marrow development	1	218.9×	0.012	ASXL1
peripheral nervous system neuron development	1	218.9×	0.012	RUNX1
podocyte development	1	218.9×	0.012	ASXL1
amelogenesis	1	200.6×	0.013	CSF3R
positive regulation of gene expression via chromosomal CpG island demethylation	1	172.0×	0.014	TET2
dendritic cell differentiation	1	150.5×	0.016	FLT3

Therapeutics

Drug target analysis

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

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
RUNX1	APOMORPHINE HYDROCHLORIDE
TET2	VADADUSTAT
FLT3	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FLT3	143	4
TET2	3	4
RUNX1	2	4
SETBP1	0	0
CSF3R	0	0
ASXL1	0	0
MFSD11	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
VADADUSTAT	4	TET2
PANOBINOSTAT	4	TET2
DEFEROXAMINE	4	TET2
PONATINIB	4	FLT3
AFATINIB	4	FLT3
FEDRATINIB	4	FLT3
TIVOZANIB	4	FLT3
AXITINIB	4	FLT3
SORAFENIB	4	FLT3
NERATINIB	4	FLT3
INFIGRATINIB PHOSPHATE	4	FLT3
INFIGRATINIB	4	FLT3
IBRUTINIB	4	FLT3
PALBOCICLIB	4	FLT3
REGORAFENIB	4	FLT3
ENTRECTINIB	4	FLT3
PACRITINIB	4	FLT3
FOSTAMATINIB	4	FLT3
QUIZARTINIB DIHYDROCHLORIDE	4	FLT3
CABOZANTINIB	4	FLT3
CERITINIB	4	FLT3
VANDETANIB	4	FLT3
NILOTINIB	4	FLT3
BOSUTINIB	4	FLT3
FILGOTINIB	4	FLT3
ABEMACICLIB	4	FLT3
GILTERITINIB	4	FLT3
BRIGATINIB	4	FLT3
PEXIDARTINIB	4	FLT3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FLT3	3,132	Binding:3096, Functional:24, ADMET:8, Toxicity:4
TET2	24	Binding:24
RUNX1	20	Binding:17, Functional:3
CSF3R	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FLT3	2.7.10.1	receptor 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
FLT3	3,132

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

26 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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
VADADUSTAT	4	TET2
PANOBINOSTAT	4	TET2
DEFEROXAMINE	4	TET2
AFATINIB	4	FLT3
FEDRATINIB	4	FLT3
TIVOZANIB	4	FLT3
AXITINIB	4	FLT3
SORAFENIB	4	FLT3
INFIGRATINIB PHOSPHATE	4	FLT3
INFIGRATINIB	4	FLT3
IBRUTINIB	4	FLT3
PALBOCICLIB	4	FLT3
REGORAFENIB	4	FLT3
FOSTAMATINIB	4	FLT3
QUIZARTINIB DIHYDROCHLORIDE	4	FLT3
CABOZANTINIB	4	FLT3
CERITINIB	4	FLT3
VANDETANIB	4	FLT3
NILOTINIB	4	FLT3
BOSUTINIB	4	FLT3
FILGOTINIB	4	FLT3
ABEMACICLIB	4	FLT3
GILTERITINIB	4	FLT3
BRIGATINIB	4	FLT3
PEXIDARTINIB	4	FLT3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	RUNX1, TET2, FLT3
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	CSF3R
D	Druggable family + AlphaFold only, no drug	1	MFSD11
E	Difficult family or no structure, no drug	2	SETBP1, ASXL1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ASXL1	0	TET2
SETBP1	0	—
CSF3R	3	—
MFSD11	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 33.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	12
PHASE1	12
Not specified	5
PHASE1/PHASE2	3
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03289910	PHASE2	ACTIVE_NOT_RECRUITING	Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia
NCT03862157	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT04761770	PHASE2	ACTIVE_NOT_RECRUITING	Study of a Geriatric Assessment to Plan a Treatment Approach for Older People With Various Blood Disorders
NCT06523556	PHASE1/PHASE2	RECRUITING	Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia
NCT07238712	PHASE2	RECRUITING	Optimization of Post-transplantation Benadamustine and Cyclophosphamide in Patients With High-risk Myeloid Malignancies and a Partially Mismatched Donor
NCT07468916	PHASE2	NOT_YET_RECRUITING	Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
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
NCT00381550	PHASE2	COMPLETED	3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia
NCT00387426	PHASE2	TERMINATED	Sunitinib in Treating Patients With Idiopathic Myelofibrosis
NCT00397813	PHASE2	COMPLETED	Fludarabine Phosphate and Total Body Irradiation Followed by a Donor Peripheral Stem Cell Transplant in Treating Patients With Myelodysplastic Syndromes or Myeloproliferative Disorders
NCT00489203	PHASE2	COMPLETED	Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
NCT00509249	PHASE2	TERMINATED	Aflibercept in Treating Patients With Myelodysplastic Syndromes
NCT02092324	PHASE2	COMPLETED	Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia
NCT02210858	PHASE1/PHASE2	COMPLETED	Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders
NCT05549661	PHASE1	RECRUITING	Onvansertib for the Treatment of Recurrent or Refractory Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome/MPN Overlap Neoplasms
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
NCT00060372	PHASE1	COMPLETED	Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer
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
NCT00890747	PHASE1	COMPLETED	Sunitinib Malate in Treating HIV-Positive Patients With Cancer Receiving Antiretroviral Therapy
NCT01231919	PHASE1	COMPLETED	MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia
NCT01484015	PHASE1	COMPLETED	Prolonged or Standard Infusion of Cefepime Hydrochloride in Treating Patients With Febrile Neutropenia
NCT02564536	PHASE1	WITHDRAWN	Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)
NCT03878524	PHASE1	TERMINATED	Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial
NCT03964506	EARLY_PHASE1	RECRUITING	Hyperbaric Oxygen Therapy and Allogeneic Peripheral Blood Stem Cell (PBSC) Transplant
NCT00856388	Not specified	COMPLETED	Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders
NCT00898079	Not specified	COMPLETED	Collecting and Storing Malignant, Borderline Malignant Neoplasms, and Related Samples From Young Patients With Cancer
NCT01053494	Not specified	COMPLETED	Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer
NCT01233921	Not specified	COMPLETED	Palifermin in Preventing Chronic Graft-Versus-Host Disease in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer
NCT01558778	Not specified	WITHDRAWN	Mechanical Stimulation in Preventing Bone Density Loss in Patients Undergoing Donor Stem Cell Transplant

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	5
DACOMITINIB ANHYDROUS	4	3
ALEMTUZUMAB	4	1
AXATILIMAB	4	1
BECLOMETHASONE DIPROPIONATE	4	1
BELINOSTAT	4	1
CEFEPIME HYDROCHLORIDE	4	1
CELECOXIB	4	1
COBIMETINIB	4	1
COPANLISIB	4	1
DAROLUTAMIDE	4	1
ENASIDENIB	4	1
ENTRECTINIB	4	1
IDELALISIB	4	1
LORLATINIB	4	1
NERATINIB	4	1
PACRITINIB	4	1
PALIFERMIN	4	1
PONATINIB	4	1
ROPEGINTERFERON ALFA-2B	4	1
RUXOLITINIB	4	1
SUNITINIB MALATE	4	1
TOPOTECAN	4	1
VISMODEGIB	4	1
VELIPARIB	3	2
PEVONEDISTAT	3	1
TIPIFARNIB	3	1
TRIAPINE	3	1
ONVANSERTIB	2	1
CHEMBL3109278	0	1

Precision-medicine subtype map (CIViC)

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

Molecular subtype	Therapy	Effect	Level	CIViC
NTRK2 R458G	Larotrectinib + Entrectinib	Sensitivity/Response	CIViC C	EID8625