JAK2 V617F é um dos três motoristas que definem a mielofibrose primária (~50-60%; CALR ~25%,...
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| ID | BMA-JAK2-V617F-PMF |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-PMF |
| Fontes | SRC-CIVIC SRC-COMFORT-I-VERSTOVSEK-2012 SRC-DIPSS-PLUS-GANGAT-2011 SRC-ESMO-MPN-2015 SRC-JAKARTA2-HARRISON-2017 SRC-MOMENTUM-VERSTOVSEK-2023 SRC-NCCN-MPN-2025 |
Fatos de ação
| Biomarcador | BIO-JAK2 |
|---|---|
| Variante | V617F (exon 14 — presente em ~50-60% da mielofibrose primária) |
| Doença | DIS-PMF |
| Nível ESCAT | IA |
| Combinações recomendadas | ruxolitinib monotherapy (intermediate-2 / high-risk per SRC-COMFORT-I-VERSTOVSEK-2012, SRC-NCCN-MPN-2025), fedratinib monotherapy (post-ruxolitinib failure per SRC-JAKARTA2-HARRISON-2017), momelotinib monotherapy (MF + anemia per SRC-MOMENTUM-VERSTOVSEK-2023), allogeneic HCT (transplant-eligible higher-risk per SRC-NCCN-MPN-2025, SRC-DIPSS-PLUS-GANGAT-2011) |
| Resumo das provas | JAK2 V617F is one of three defining drivers in primary myelofibrosis (~50-60%; CALR ~25%, MPL ~5-10%, triple-negative ~10%) and a WHO 2022 / ICC 2022 major diagnostic criterion (per SRC-NCCN-MPN-2025, SRC-ESMO-MPN-2015). Treatment by symptom burden / risk score (DIPSS- Plus, MIPSS70, MIPSS70+v2): symptomatic intermediate/high-risk → ruxolitinib (COMFORT-I Verstovsek 2012 — 41.9% spleen response vs 0.7% placebo, OS benefit on extended follow-up); fedratinib for ruxolitinib-failure (JAKARTA2 Harrison 2017 — 31% spleen response in RUX-failure); momelotinib for anemic patients (MOMENTUM Verstovsek 2023 — superior anemia + symptom benefit vs danazol). Allogeneic HCT is the only curative therapy and is recommended for transplant- eligible higher-risk patients per SRC-NCCN-MPN-2025. |
Notas
ESCAT IA / OncoKB Level 1 — JAK-inhibitor therapy is genotype- agnostic (works for V617F, CALR, MPL, and triple-negative MF) because it targets downstream activated JAK-STAT signaling rather than the upstream mutation. Risk stratification (DIPSS-Plus, MIPSS70+v2) considers V617F allele burden indirectly via cytogenetics / molecular high-risk features. Source-gap: SRC-NCCN-MPN-2025 STUB.
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Não há referências reversas encontradas no corpus YAML.