Chronic neutrophilic leukemia

Summary

Chronic neutrophilic leukemia (MONDO:0019451) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver) and 22 clinical trials. Molecularly, CSF3R T618I confers sensitivity to Ruxolitinib in Chronic Neutrophilic Leukemia (CIViC Level C). Top therapeutic interventions include foscarnet, tacrolimus anhydrous, and beclomethasone dipropionate.

At a glance

• Classification: Cancer
• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• Clinical trials: 22
• 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	chronic neutrophilic leukemia
Mondo ID	MONDO:0019451
EFO	EFO:1000179
MeSH	D015467
Orphanet	86829
DOID	DOID:0080187
ICD-11	426734182
NCIT	C3179
SNOMED CT	188734009
UMLS	C0023481
MedGen	6061
GARD	0010585
Is cancer (heuristic)	yes

Also known as: chronic neutrophilic leukemia · CNL · neutrophilic leukaemia · neutrophilic leukemia

Data availability: 2 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 › chronic leukemia › chronic neutrophilic leukemia

Related subtypes (7): prolymphocytic leukemia, chronic monocytic leukemia, B-cell chronic lymphocytic leukemia, chronic eosinophilic leukemia, T-cell large granular lymphocyte leukemia, aggressive NK-cell leukemia, chronic myelomonocytic 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CSF3R	LoF	AML,BLADDER,HNSC	CIViC #1239

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
civic_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CSF3R	HGNC:2439	ENSG00000119535	Q99062	Granulocyte colony-stimulating factor receptor	civic_evidence

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.

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)
CSF3R	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd

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
blood	1
granulocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF3R	192	broad	marker	granulocyte, monocyte, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CSF3R	3,315

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSF3R	Q99062	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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 CSF3 (G-CSF)	1	571.0×	0.003	CSF3R
Other interleukin signaling	1	475.8×	0.003	CSF3R
Inactivation of CSF3 (G-CSF) signaling	1	439.2×	0.003	CSF3R
Transcriptional regulation of granulopoiesis	1	125.5×	0.008	CSF3R

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
regulation of myeloid cell differentiation	1	3370.4×	0.002	CSF3R
amelogenesis	1	1404.3×	0.003	CSF3R
neutrophil chemotaxis	1	285.6×	0.009	CSF3R
defense response	1	216.1×	0.009	CSF3R
cytokine-mediated signaling pathway	1	130.6×	0.012	CSF3R
cell adhesion	1	37.5×	0.034	CSF3R
positive regulation of cell population proliferation	1	33.6×	0.034	CSF3R
signal transduction	1	16.1×	0.062	CSF3R

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Fedratinib.

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSF3R	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CSF3R	3	Binding:3

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	1	CSF3R
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
CSF3R	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE2	6
PHASE1	5
PHASE3	2
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
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
NCT01305200	PHASE3	COMPLETED	Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant
NCT03862157	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Azacitidine, Venetoclax, and Pevonedistat in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT05177211	PHASE2	ACTIVE_NOT_RECRUITING	Fedratinib in Myelodysplastic /Myeloproliferative Neoplasms (MDS/MPNs) and Chronic Neutrophilic Leukemia (CNL)
NCT00489203	PHASE2	COMPLETED	Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
NCT00795769	PHASE2	COMPLETED	Ondansetron in Preventing Nausea and Vomiting in Patients Undergoing Stem Cell Transplant
NCT01159067	PHASE2	TERMINATED	Deferasirox for Treating Patients Who Have Undergone Allogeneic Stem Cell Transplant and Have Iron Overload
NCT01384513	PHASE2	COMPLETED	A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies
NCT02092324	PHASE2	COMPLETED	Ruxolitinib Phosphate in Treating Patients With Chronic Neutrophilic Leukemia or Atypical Chronic Myeloid Leukemia
NCT00025415	PHASE1	COMPLETED	Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction
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
NCT07071155	EARLY_PHASE1	RECRUITING	Momelotinib in Combination With Hypomethylating Agent for Chronic Phase Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Chronic Neutrophilic Leukemia
NCT01199562	Not specified	ACTIVE_NOT_RECRUITING	Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant
NCT00112593	Not specified	COMPLETED	Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer
NCT00408681	Not specified	COMPLETED	Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell 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
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
FOSCARNET	4	4
TACROLIMUS ANHYDROUS	4	2
BECLOMETHASONE DIPROPIONATE	4	1
CEFEPIME HYDROCHLORIDE	4	1
DEFERASIROX	4	1
FEDRATINIB	4	1
GANCICLOVIR	4	1
LITHIUM CARBONATE	4	1
MOMELOTINIB	4	1
PALIFERMIN	4	1
RUXOLITINIB	4	1
VALGANCICLOVIR	4	1
PEVONEDISTAT	3	1
CHEMBL1319520	0	1
CHEMBL4465517	0	1
CHEMBL1201736	0	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 1 predictive associations from 2 curated evidence items; also 1 diagnostic.

Molecular subtype	Therapy	Effect	Level	CIViC
CSF3R T618I	Ruxolitinib	Sensitivity/Response	CIViC C	EID6381 +1