Myelofibrosis with myeloid metaplasia

disease

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Also known as MMM

Summary

Myelofibrosis with myeloid metaplasia (MONDO:0800305) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include pomalidomide.

At a glance

Cohort genes: 1
ClinVar variants: 2
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myelofibrosis with myeloid metaplasia
Mondo ID	MONDO:0800305
ICD-11	673220507
GARD	0026490
Is cancer (heuristic)	no

Also known as: MMM

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › aplastic anemia › acquired aplastic anemia › primary myelofibrosis › myelofibrosis with myeloid metaplasia

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

2 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
14165	NM_005373.3(MPL):c.1543_1544delinsAA (p.Trp515Lys)	MPL	Pathogenic	no assertion criteria provided
14164	NM_005373.3(MPL):c.1544G>T (p.Trp515Leu)	MPL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MPL	Orphanet:3318	Essential thrombocythemia
MPL	Orphanet:3319	Congenital amegakaryocytic thrombocytopenia
MPL	Orphanet:397692	Hereditary isolated aplastic anemia
MPL	Orphanet:71493	Familial thrombocytosis
MPL	Orphanet:824	Primary myelofibrosis

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
MPL	HGNC:7217	ENSG00000117400	P40238	Thrombopoietin receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MPL	Thrombopoietin receptor	Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation.

Protein-family classification

Druggable: 1 · 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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MPL	Antibody/Immunoglobulin	yes		Long_hematopoietin_rcpt_CS, FN3_dom, Ig-like_fold

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
male germ line stem cell (sensu Vertebrata) in testis	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MPL	166	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, mononuclear cell, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MPL	1,039

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MPL	P40238	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Platelet Aggregation (Plug Formation)	1	439.2×	0.002	MPL

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
basophil homeostasis	1	16852.0×	4e-04	MPL
positive regulation of platelet formation	1	8426.0×	4e-04	MPL
monocyte homeostasis	1	5617.3×	4e-04	MPL
eosinophil homeostasis	1	5617.3×	4e-04	MPL
thrombopoietin-mediated signaling pathway	1	2106.5×	8e-04	MPL
positive regulation of lymphocyte proliferation	1	1872.4×	8e-04	MPL
neutrophil homeostasis	1	1532.0×	8e-04	MPL
platelet formation	1	702.2×	0.002	MPL
cellular response to hypoxia	1	121.2×	0.008	MPL

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
MPL	LUSUTROMBOPAG

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MPL	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LUSUTROMBOPAG	4	MPL
ELTROMBOPAG	4	MPL

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MPL	23	Functional:15, Binding:7, ADMET:1

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).

Chemical tractability of cohort targets

2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
LUSUTROMBOPAG	4	MPL
ELTROMBOPAG	4	MPL

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MPL
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: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00463385	PHASE2	COMPLETED	A Phase II Study of Pomalidomide in Myelofibrosis With Myeloid Metaplasia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
POMALIDOMIDE	4	1
CHEMBL15720	0	1
CHEMBL2093113	0	1

Cohort genes: MPL
Drugs: Pomalidomide