Las mutaciones activadoras JAK3 se detectan en ~35% de los subtipos ATLL agresivos (agudo y l...
Vista determinista de la entidad fuente YAML. La autoridad clínica sigue con los ID de fuente citados y estado de firma del revisor.
| ID | BMA-JAK3-ATLL |
|---|---|
| Tipo | Relevancia terapéutica |
| Situación | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Enfermedades | DIS-ATLL |
| Fuentes | SRC-ESMO-PTCL-2024 |
Hechos relativos a la posibilidad de adoptar medidas
| Biomarcador | BIO-JAK3 |
|---|---|
| Variante | mutación activadora JAK3 (A572V, A573V, M511I más común) — leucemia/linfoma de células T adultas (ATLL); subtipos predominantemente agresivos (aguda y linfoma) |
| Enfermedad | DIS-ATLL |
| El nivel de ESCAT | IIA |
| Combinaciones recomendadas | Ruxolitinib 20 mg PO BID (investigación en ATLL; dosis por aprobación MF/GVHD; subgrupo mutante JAK3; ensayo clínico preferido), mogamulizumab 1 mg/kg IV (aprobado para CTCL en EE.UU.; utilizado fuera de la etiqueta para ATLL, CCR4-enfocado, no específico JAH3) quimioterapia VCAP-AMP-VECP (ATLL agresivo estándar según las directrices japonesas) |
| Resumen de las pruebas | 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.
Utilizado por
No se encuentran referencias inversas en el corpus YAML.