Myeloproliferative neoplasm

Summary

Myeloproliferative neoplasm (MONDO:0020076) is a cancer (an umbrella term covering 13 Mondo subtypes) with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 418 clinical trials. Molecularly, PDGFRB Fusion confers sensitivity to Imatinib in Myeloproliferative Neoplasm (CIViC Level A); 3 further subtype–drug associations are mapped below. Top therapeutic interventions include fludarabine phosphate, busulfan, and ivosidenib.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 13 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 418
• Precision-medicine evidence (CIViC): 4 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	3.07	Europe	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	myeloproliferative neoplasm
Mondo ID	MONDO:0020076
EFO	EFO:0002428
Orphanet	98274
DOID	DOID:2226
NCIT	C4345
SNOMED CT	425333006
UMLS	C1292778
MedGen	220955
GARD	0009319
MedDRA	10028576
Anatomy (UBERON)	UBERON:0002371
Is cancer (heuristic)	yes

Also known as: chronic myeloproliferative disease · chronic myeloproliferative disorder · chronic myeloproliferative disorders · chronic myeloproliferative neoplasm · CMPD · MPD · MPN · myeloproliferative disorder · myeloproliferative neoplasm · myeloproliferative neoplasm, chronic · myeloproliferative neoplasms · myeloproliferative tumor · myeloproliferative tumour

Data availability: 1 ClinVar variant · 11 cell lines.

Disease family

An umbrella term covering 13 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 › myeloid neoplasm › myeloproliferative neoplasm

Related subtypes (3): mast cell neoplasm, plasma cell myeloma, CD4+/CD56+ hematodermic neoplasm

Subtypes (13): myeloid leukemia, essential thrombocythemia, myelodysplastic/myeloproliferative neoplasm, therapy-related myeloid neoplasm, transient myeloproliferative syndrome, primary myelofibrosis, myeloproliferative disease, autosomal recessive, thrombocytopenia 6, chronic eosinophilic leukemia, chronic neutrophilic leukemia, myeloproliferative neoplasm, unclassifiable, erythroid neoplasm, myelofibrosis

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2674591	NM_181552.4(CUX1):c.3820A>G (p.Ile1274Val)	CUX1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CUX1	LoF	BRCA,GB,LUAD,LUSC,MEL,PAAD,WDTC

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CUX1	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CUX1	HGNC:2557	ENSG00000257923	P39880	Homeobox protein cut-like 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CUX1	Homeobox protein cut-like 1	Transcription factor involved in the control of neuronal differentiation in the brain.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CUX1	Transcription factor	no		HD, CUT_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CUX1	297	ubiquitous	marker	secondary oocyte, buccal mucosa cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUX1	2,356

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CUX1	P39880	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by cytosolic FGFR1 fusion mutants	1	634.4×	0.008	CUX1
Signaling by FGFR1 in disease	1	292.8×	0.008	CUX1
Intra-Golgi traffic	1	259.6×	0.008	CUX1
Intra-Golgi and retrograde Golgi-to-ER traffic	1	104.8×	0.014	CUX1
Membrane Trafficking	1	37.1×	0.029	CUX1
Vesicle-mediated transport	1	34.8×	0.029	CUX1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of dendrite morphogenesis	1	887.0×	0.004	CUX1
intra-Golgi vesicle-mediated transport	1	526.6×	0.004	CUX1
negative regulation of transcription by RNA polymerase II	1	17.7×	0.075	CUX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	CUX1

Therapeutics

Drugs indicated for this disease

0 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Amphotericin B	Phase 3 (in late-stage trials)
Cytarabine	Phase 3 (in late-stage trials)
Decitabine	Phase 3 (in late-stage trials)
Etoposide	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine Phosphate	Phase 3 (in late-stage trials)
Idarubicin	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Nystatin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aldesleukin, Alemtuzumab, Busulfan, Carboplatin, Fludarabine, Interferon Alfa, Melphalan, Methylprednisolone, Mycophenolate Mofetil, Prednisone, Sargramostim, Tacrolimus Anhydrous, Tanespimycin, Thiotepa.

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CUX1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	CUX1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CUX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 418.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	134
Not specified	134
PHASE1	73
PHASE1/PHASE2	43
PHASE3	26
EARLY_PHASE1	4
PHASE4	2
PHASE2/PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06290765	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Ropeginterferon Alfa 2b (P1101) for Patients With Polycythemia Vera
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT02521493	PHASE3	ACTIVE_NOT_RECRUITING	Response-Based Chemotherapy in Treating Newly Diagnosed Acute Myeloid Leukemia or Myelodysplastic Syndrome in Younger Patients With Down Syndrome
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT04717414	PHASE3	ACTIVE_NOT_RECRUITING	An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions
NCT06468033	PHASE3	RECRUITING	P1101 in Treating Patients With Early PMF or Overt PMF at Low or Intermediate-1 Risk
NCT06740916	PHASE3	RECRUITING	Long-term Efficacy of Once Daily Versus Twice Daily Aspirin in High-risk MPN Patients With Aspirin Resistance
NCT00002742	PHASE3	COMPLETED	Antifungal Therapy for Fever and Neutropenia in Patients Receiving Treatment for Hematologic Cancer
NCT00003600	PHASE3	COMPLETED	Epoetin Alfa in Treating Anemia in Patients Who Are Receiving Chemotherapy
NCT00003687	PHASE3	COMPLETED	Treatment for Chronic Pain in Patients With Advanced Cancer
NCT00003816	PHASE2/PHASE3	COMPLETED	Combination Chemotherapy and Donor Stem Cell Transplant in Treating Patients With Aplastic Anemia or Hematologic Cancer
NCT00005805	PHASE3	COMPLETED	St. John’s Wort in Relieving Fatigue in Patients Undergoing Chemotherapy or Hormone Therapy for Cancer
NCT00006083	PHASE3	COMPLETED	Dalteparin to Prevent Complications in Cancer Patients Receiving Chemotherapy Through a Catheter
NCT00006348	PHASE3	COMPLETED	Ondansetron in Treating Patients With Advanced Cancer and Chronic Nausea and Vomiting Not Caused by Cancer Treatment
NCT00075816	PHASE3	COMPLETED	Peripheral Blood Stem Cell Transplant vs Bone Marrow Transplant in Individuals With Hematologic Cancers (BMT CTN 0201)
NCT00324324	PHASE3	TERMINATED	Moxifloxacin in Preventing Bacterial Infections in Patients Who Have Undergone Donor Stem Cell Transplant
NCT00438958	PHASE3	COMPLETED	Sibling Donor Peripheral Stem Cell Transplant or Sibling Donor Bone Marrow Transplant in Treating Patients With Hematologic Cancers or Other Diseases
NCT00516503	PHASE3	COMPLETED	Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00666211	PHASE3	COMPLETED	Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain
NCT00719563	PHASE3	COMPLETED	American Ginseng in Treating Patients With Fatigue Caused by Cancer
NCT00750009	PHASE3	COMPLETED	Personalized Information or Basic Information in Helping Patients Make Decisions About Participating in a Clinical Trial
NCT00755040	PHASE3	COMPLETED	Cyclosporine Eye Drops in Preventing Graft-Versus-Host Disease of the Eye in Patients Who Have Undergone Donor Stem Cell Transplant for Hematologic Cancer or Bone Marrow Failure Disorder
NCT00782145	PHASE3	COMPLETED	A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families
NCT00952289	PHASE3	COMPLETED	COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial
NCT00967343	PHASE2/PHASE3	TERMINATED	Efficacy and Safety of a Donor Lymphocyte Preparation Depleted of Functional Host Alloreactive T-cells (ATIR) in Patients Undergoing a Peripheral Blood Stem Cell Transplant From a Related, Haploidentical Donor
NCT01231412	PHASE3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01366612	PHASE3	TERMINATED	Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation
NCT01951885	PHASE3	COMPLETED	Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention
NCT02611973	PHASE3	UNKNOWN	Hydroxyurea Versus Aspirin and Hydroxyurea in Essential Thrombocythemia
NCT03808805	PHASE3	COMPLETED	Aprepitant Versus Hydroxyzine in Persistent Aquagenic Pruritus for Patients With Myeloproliferative Neoplasms
NCT00544115	PHASE2	ACTIVE_NOT_RECRUITING	Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders
NCT01761968	PHASE2	ACTIVE_NOT_RECRUITING	Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms
NCT02506933	PHASE2	ACTIVE_NOT_RECRUITING	Multi-antigen CMV-MVA Triplex Vaccine in Reducing CMV Complications in Patients Previously Infected With CMV and Undergoing Donor Hematopoietic Cell Transplant
NCT03192397	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant
NCT03314974	PHASE2	RECRUITING	Myeloablative Allo HSCT With Related or Unrelated Donor for Heme Disorders
NCT03386513	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of IMGN632 in Patients With Untreated BPDCN and Relapsed/Refractory BPDCN
NCT03471260	PHASE1/PHASE2	RECRUITING	Ivosidenib and Venetoclax With or Without Azacitidine in Treating Patients With IDH1 Mutated Hematologic Malignancies
NCT03589729	PHASE2	RECRUITING	Dexrazoxane Hydrochloride in Preventing Heart-Related Side Effects of Chemotherapy in Participants With Blood Cancers
NCT03622788	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant
NCT03779854	PHASE2	RECRUITING	Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUDARABINE PHOSPHATE	4	69
BUSULFAN	4	5
IVOSIDENIB	4	5
RUXOLITINIB	4	5
FEDRATINIB	4	4
PACRITINIB	4	4
ALDESLEUKIN	4	3
AMITRIPTYLINE	4	3
BENDAMUSTINE HYDROCHLORIDE	4	3
CLADRIBINE	4	3
DEXTROMETHORPHAN	4	3
ENASIDENIB	4	3
LUSPATERCEPT	4	3
MELPHALAN	4	3
ONDANSETRON	4	3
ALEMTUZUMAB	4	2
CEDAZURIDINE	4	2
EDETATE CALCIUM DISODIUM MONOHYDRATE	4	2
GEMTUZUMAB OZOGAMICIN	4	2
LETERMOVIR	4	2
MORPHINE SULFATE	4	2
MOXIFLOXACIN HYDROCHLORIDE	4	2
OLUTASIDENIB	4	2
PEMIGATINIB	4	2
POMALIDOMIDE	4	2
ROPEGINTERFERON ALFA-2B	4	2
THIOTEPA	4	2
ALCOHOL	4	1
ALLOPURINOL	4	1
AMIFOSTINE	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 4 predictive associations from 5 curated evidence items; also 2 oncogenic.

Molecular subtype	Therapy	Effect	Level	CIViC
PDGFRB Fusion	Imatinib	Sensitivity/Response	CIViC A	EID11272 +1
FIP1L1::PDGFRA Fusion	Imatinib	Sensitivity/Response	CIViC A	EID11273
ZMYM2::FGFR1 Fusion	Midostaurin	Sensitivity/Response	CIViC C	EID1104
ETV6::FGFR3 Fusion	Midostaurin	Sensitivity/Response	CIViC D	EID10409