B-lymphoblastic leukemia/lymphoma with hyperdiploidy

Summary

B-lymphoblastic leukemia/lymphoma with hyperdiploidy (MONDO:0035943) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record).

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	B-lymphoblastic leukemia/lymphoma with hyperdiploidy
Mondo ID	MONDO:0035943
Orphanet	585936
DOID	DOID:0080646
NCIT	C80335
UMLS	C2698311
MedGen	397154
GARD	0022345
Is cancer (heuristic)	yes

Data availability: 1 ClinVar variant.

Disease family

Classification path: 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 › lymphoid neoplasm › precursor lymphoblastic lymphoma/leukemia › B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality › B-lymphoblastic leukemia/lymphoma with hyperdiploidy

Related subtypes (5): B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2), B-lymphoblastic leukemia/lymphoma with t(v;11q23.3), B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1), B-lymphoblastic leukemia/lymphoma with hypodiploidy, B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3)

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
503532	NM_005188.4(CBL):c.1676G>T (p.Arg559Leu)	CBL	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
CBL	LoF	ALL,AML,ESCA	CIViC #778

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CBL	Orphanet:363972	Noonan syndrome-like disorder with juvenile myelomonocytic leukemia
CBL	Orphanet:648	Noonan syndrome
CBL	Orphanet:86834	Juvenile myelomonocytic leukemia
CBL	Orphanet:98850	Aggressive systemic mastocytosis

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
CBL	HGNC:1541	ENSG00000110395	P22681	E3 ubiquitin-protein ligase CBL	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CBL	E3 ubiquitin-protein ligase CBL	E3 ubiquitin-protein ligase that acts as a negative regulator of many signaling pathways by mediating ubiquitination of cell surface receptors.

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)
CBL	Transcription factor	no	2.3.2.27	Znf_RING, Adaptor_Cbl_N_hlx, UBA-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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
trigeminal ganglion	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CBL	271	ubiquitous	marker	primordial germ cell in gonad, trigeminal ganglion, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CBL	4,575

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CBL	P22681	33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. 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 EGFRvIII in Cancer	1	2284.0×	0.004	CBL
Signaling by Ligand-Responsive EGFR Variants in Cancer	1	1903.3×	0.004	CBL
FLT3 signaling by CBL mutants	1	1631.4×	0.004	CBL
Interleukin-6 family signaling	1	1427.5×	0.004	CBL
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1	1	1268.9×	0.004	CBL
Signaling by EGFR in Cancer	1	1142.0×	0.004	CBL
Signaling by FGFR3	1	1142.0×	0.004	CBL
FLT3 signaling in disease	1	1142.0×	0.004	CBL
Signaling by FGFR4	1	1038.2×	0.004	CBL
Listeria monocytogenes entry into host cells	1	1038.2×	0.004	CBL
Interleukin-6 signaling	1	951.7×	0.004	CBL
Signaling by FGFR1	1	815.7×	0.004	CBL
InlB-mediated entry of Listeria monocytogenes into host cell	1	761.3×	0.004	CBL
Spry regulation of FGF signaling	1	713.8×	0.004	CBL
Constitutive Signaling by EGFRvIII	1	713.8×	0.004	CBL
Negative regulation of FLT3	1	713.8×	0.004	CBL
Regulation of KIT signaling	1	601.0×	0.004	CBL
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	571.0×	0.004	CBL
Signaling by PTK6	1	543.8×	0.004	CBL
Signaling by Non-Receptor Tyrosine Kinases	1	543.8×	0.004	CBL
Negative regulation of MET activity	1	519.1×	0.004	CBL
Regulation of signaling by CBL	1	496.5×	0.004	CBL
Negative regulation of FGFR3 signaling	1	439.2×	0.004	CBL
Negative regulation of FGFR4 signaling	1	407.9×	0.004	CBL
Signaling by FGFR2	1	407.9×	0.004	CBL
Negative regulation of FGFR1 signaling	1	368.4×	0.004	CBL
Negative regulation of FGFR2 signaling	1	368.4×	0.004	CBL
EGFR downregulation	1	346.1×	0.004	CBL
Signaling by FGFR	1	346.1×	0.004	CBL
FLT3 Signaling	1	346.1×	0.004	CBL

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 platelet-derived growth factor receptor-alpha signaling pathway	1	5617.3×	0.004	CBL
regulation of Rap protein signal transduction	1	4213.0×	0.004	CBL
ubiquitin-dependent endocytosis	1	1872.4×	0.005	CBL
positive regulation of receptor-mediated endocytosis	1	802.5×	0.005	CBL
negative regulation of epidermal growth factor receptor signaling pathway	1	766.0×	0.005	CBL
cellular response to platelet-derived growth factor stimulus	1	648.1×	0.005	CBL
mast cell degranulation	1	624.1×	0.005	CBL
response to gamma radiation	1	581.1×	0.005	CBL
negative regulation of T cell activation	1	526.6×	0.005	CBL
positive regulation of epidermal growth factor receptor signaling pathway	1	495.6×	0.005	CBL
response to testosterone	1	468.1×	0.005	CBL
response to starvation	1	468.1×	0.005	CBL
cellular response to nerve growth factor stimulus	1	468.1×	0.005	CBL
symbiont entry into host cell	1	401.2×	0.005	CBL
negative regulation of T cell receptor signaling pathway	1	366.4×	0.005	CBL
protein monoubiquitination	1	343.9×	0.005	CBL
response to activity	1	324.1×	0.005	CBL
protein K63-linked ubiquitination	1	267.5×	0.006	CBL
protein autoubiquitination	1	234.1×	0.007	CBL
male gonad development	1	156.0×	0.010	CBL
response to ethanol	1	146.5×	0.010	CBL
cytokine-mediated signaling pathway	1	130.6×	0.010	CBL
cellular response to hypoxia	1	121.2×	0.011	CBL
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.016	CBL
ubiquitin-dependent protein catabolic process	1	74.2×	0.016	CBL
protein stabilization	1	66.9×	0.017	CBL
DNA damage response	1	53.5×	0.021	CBL
protein ubiquitination	1	41.4×	0.026	CBL
negative regulation of apoptotic process	1	34.8×	0.030	CBL
signal transduction	1	16.1×	0.062	CBL

Therapeutics

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
CBL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CBL	4	Binding:2, Toxicity:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CBL	2.3.2.27	RING-type E3 ubiquitin transferase

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	CBL

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)
CBL	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.