STAT5B
Overview
STAT5B (Signal Transducer and Activator of Transcription 5B) is a transcription factor downstream of JAK kinases, activated by cytokines including IL-2 and growth hormone. Gain-of-function mutations in STAT5B (notably N642H and I704L) are found in T-cell lymphomas and leukemias, driving constitutive JAK-STAT signaling and resistance to apoptosis. STAT5B I704L is a recurrent hotspot in gamma-delta T-cell lymphoma.
Alterations observed in the corpus
- STAT5B I704L mutation identified in a patient with T-cell lymphoblastic lymphoma/leukemia (T-BLL) in the PIPseq pediatric precision sequencing program (n=101, Columbia University); co-occurring with KRAS V14I and JAK1 K1026E. Designated as a BCL2/BCL-XL inhibitor target. PMID:28007021
- The same STAT5B I704L variant was separately diagnostic of gamma-delta T-cell lymphoma (identified by isochromosome 7q + STAT5B I704L co-occurrence). PMID:28007021
Cancer types (linked)
- BLL (T-cell subtype / T-ALL): STAT5B I704L is a therapeutically relevant mutation; BCL2/BCL-XL inhibitors (venetoclax, navitoclax) are proposed targets. PMID:28007021
- Gamma-delta T-cell lymphoma: STAT5B I704L is a diagnostic marker in combination with isochromosome 7q. PMID:28007021
Co-occurrence and mutual exclusivity
- Co-occurred with KRAS V14I and JAK1 K1026E in one T-BLL case; this combination drives multi-pathway activation (RAS + JAK-STAT). PMID:28007021
Therapeutic relevance
- BCL2/BCL-XL inhibitors designated as targeted therapy for STAT5B I704L-mutant T-BLL in the PIPseq cohort. PMID:28007021
Open questions
- Clinical efficacy of BCL2/BCL-XL inhibition in STAT5B-mutant T-cell lymphoma/leukemia requires prospective validation. PMID:28007021
Sources
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