JAK2 mutation (V617F or exon 12)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-JAK2 |
|---|---|
| Type | Biomarker |
| Aliases | JAK2 V617FJAK2 exon 12JAK2 mutationМутація JAK2 (V617F або екзон 12) |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-MPN-2015 SRC-NCCN-MPN-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"functional_impact": "Constitutive JAK2 kinase activation through JH2-domain release → JAK-STAT signaling", "gene": "JAK2", "gene_hugo_id": "HGNC:6192", "hotspots": ["V617F (exon 14, JH2 pseudokinase domain — ~95% of PV; ~50–60% of ET / PMF)", "exon 12 (small in-frame indels — ~3% of PV; JAK2-V617F-negative PV)"], "variant_type": "missense / in-frame indel"} |
| Measurement | MethodAllele-specific PCR (V617F screen — high sensitivity LoD ~0.1% VAF) + Sanger / NGS for exon 12 if V617F-negative Unitscategorical (positive/negative); VAF reported (allele burden tracks disease) Sensitivity requirementASP / ddPCR LoD ~0.1% VAF for low-burden detection; allele burden useful for treatment monitoring |
| Actionability lookup | {"gene": "JAK2", "variant": "V617F"} |
| Related biomarkers | BIO-CALR |
Notes
Diagnostic for PV (V617F or exon 12 — together ≥98%), ET (~50–60% V617F), PMF (~50–60% V617F). Mutually exclusive with CALR and MPL. JAK2 inhibitors (ruxolitinib COMFORT-I/II; fedratinib JAKARTA-2; pacritinib PERSIST-2; momelotinib MOMENTUM) treat MF symptoms + splenomegaly across all driver genotypes. Ruxolitinib is also 1L for hydroxyurea-resistant / -intolerant PV (RESPONSE) and approved for symptomatic / high-risk ET in some jurisdictions. Allele burden reduction on therapy correlates with longer-term outcomes in PV / MF but is not a treatment switch trigger.
Used By
Actionability
BMA-JAK2-V617F-ET- JAK2 V617F is one of three defining drivers in essential thrombocythemia (~50-60%; CALR ~...BMA-JAK2-V617F-PMF- JAK2 V617F is one of three defining drivers in primary myelofibrosis (~50-60%; CALR ~25%,...BMA-JAK2-V617F-PV- JAK2 V617F is the defining driver of polycythemia vera (~95%) and a WHO 2022 / ICC 2022 m...
Biomarker
BIO-CALR- CALR mutation (exon 9)BIO-JAK3- JAK3 activating mutation
Indications
IND-PV-ANAGRELIDE-CONTINUOUS- IND-PV-ANAGRELIDE-CONTINUOUSIND-PV-PREGNANCY-PEG-IFN- IND-PV-PREGNANCY-PEG-IFN
Questionnaires
QUEST-PV-1L-STUB- Polycythemia Vera — first line