As mutações ativadoras JAK3 são detectadas em ~35% dos subtipos ATLL agressivos (agudo e lym...
Visão determinística da entidade fonte YAML. A autoridade clínica permanece com os IDs de fonte citados e estado de assinatura do revisor.
| ID | BMA-JAK3-ATLL |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-ATLL |
| Fontes | SRC-ESMO-PTCL-2024 |
Fatos de ação
| Biomarcador | BIO-JAK3 |
|---|---|
| Variante | mutação activadora JAK3 (A572V, A573V, M511I mais frequentes) — leucemia/linfoma de células T adultas (ATLL); subtipos predominantemente agressivos (aguda e linfoma) |
| Doença | DIS-ATLL |
| Nível ESCAT | IIA |
| Combinações recomendadas | ruxolitinib 20 mg PO BID (investigação em ATLL; dose por aprovação MF/GVHD; subgrupo mutante JAK3; ensaio clínico preferido), mogamulizumab 1 mg/kg IV (aprovado para CTCL nos EUA; utilizado fora do rótulo para ATLL, CCR4-alvo, não específico JAQ3), quimioterapia VCAP-AMP-VECP (ATLL agressivo padrão por diretrizes japonesas) |
| Resumo das provas | JAK3 activating mutations are detected in ~35% of aggressive ATLL subtypes (acute and lymphoma types) and activate downstream STAT3/STAT5 independent of cytokine stimulation. Ruxolitinib (JAK1/2 inhibitor; FDA-approved for myelofibrosis, PV, GVHD, CTCL) has documented activity in JAK3-mutant ATLL: case series and retrospective analyses report ORRs of 40–67% in relapsed/refractory ATLL; single-arm phase II data is limited. No FDA approval for ATLL specifically. Mogamulizumab (anti-CCR4, FDA 2018 for CTCL) is approved for relapsed/refractory CTCL and ATLL in Japan; FDA approval is CTCL only in US — CCR4 expression is present in ~90% of ATLL independent of JAK3 status. JAK3 mutation confers worse prognosis in ATLL and identifies a subset potentially responsive to JAK pathway inhibition. ESCAT IIA: biomarker predicts response to an investigational (in ATLL context) therapy class (JAK inhibitors). |
Notas
ESCAT IIA: JAK3 mutation predicts JAK inhibitor sensitivity in ATLL; no regulatory approval in ATLL for JAK inhibitors as of 2026. ATLL is caused by HTLV-1 (Human T-cell Leukemia Virus 1) and is endemic in Japan, the Caribbean, and parts of Africa/South America. Molecular landscape: JAK3 mutations (~35%), CCR4 mutations (~25%), RHOA G17V (~20%), PD-L1 amplification. Mogamulizumab (CCR4-targeted) has activity in ATLL independent of JAK3 status and is standard in Japan. Allogeneic HCT is potentially curative for fit patients with aggressive ATLL in CR. Ruxolitinib access: JAK3 mutation testing should be performed in all relapsed ATLL; if positive, ruxolitinib off-label or via compassionate use/basket trial is a reasonable option when standard therapies fail.
Usado por
Não há referências reversas encontradas no corpus YAML.