Ativação da mutação JAK3
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| ID | BIO-JAK3 |
|---|---|
| Tipo | Biomarcador |
| Alegais | Mutação JAK3Активуюча мутація JAK3 |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-ATLL DIS-MF-SEZARY |
| Fontes | SRC-ESMO-CTCL-2024 SRC-ESMO-PTCL-2024 SRC-NCCN-BCELL-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "multiple (pseudokinase + domínio de quinase)", "functional_impact":"activando", "gene": JAK3", "variant_type":", "missense activando (A572V, A573V, M511I, V722I, P132T mais frequentes)} |
| Medição | MétodoPanel de tumor NGS; sangue/medula óssea NGP para neoplasias hematológicas |
| Procura de ação | {"gene": "JAK3", "variant": "activating_mutation"} |
| Biomarcadores relacionados | BIO-JAK2 |
Notas
JAK3 is unique among JAK family kinases: it exclusively signals through the common gamma chain (γc, CD132, IL2RG), the shared receptor subunit for IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 cytokines. JAK3 is therefore predominantly expressed in T, NK, and B lymphocytes. Activating JAK3 mutations drive constitutive STAT3/STAT5 signaling independent of cytokine. Clinical contexts: (1) T-cell acute lymphoblastic leukemia (T-ALL): JAK3 mutations in ~15–20% (co-occur with NOTCH1, CDKN2A loss). (2) Adult T-cell leukemia/lymphoma (ATLL): JAK3 mutations in ~35% of aggressive subtypes. (3) Mycosis fungoides / Sézary syndrome (CTCL): JAK3/STAT3 pathway activated in ~30%. (4) Anaplastic large cell lymphoma (ALCL): JAK1/STAT3 (related pathway; JAK3 less common). Therapeutic relevance: ruxolitinib (JAK1/2 inhibitor; not JAK3-selective) is FDA-approved for CTCL (mycosis fungoides) and GVHD and has activity in ATLL (off-label). Ritlecitinib (irreversible JAK3/TEC family inhibitor, FDA 2023 for alopecia areata) is being investigated in JAK3-mutant hematologic malignancies. JAK3-selective inhibitors are theoretically preferred over JAK1/2 inhibitors to avoid myelosuppression, but clinical data in malig...
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