SETBP1
Overview
SETBP1 (SET Binding Protein 1) encodes a nuclear protein that binds the oncoprotein SET and is recurrently mutated in myeloid neoplasms. Hotspot mutations in the degron region (around D868) impair SETBP1 degradation, leading to protein accumulation and dysregulation of downstream targets. SETBP1 mutations are characteristic of atypical chronic myeloid leukemia and juvenile myelomonocytic leukemia (JMML).
Alterations observed in the corpus
- SETBP1 D868N co-occurring with PTPN11 D61Y in a 4-year-old: this combination reclassified the diagnosis from de novo AML to JMML (which subsequently evolved into AML) in the PIPseq pediatric precision sequencing program (n=101, Columbia University). PMID:28007021
Cancer types (linked)
- AML / JMML: SETBP1 D868N co-mutation with PTPN11 D61Y was diagnostically reclassifying in one pediatric case, changing management from de novo AML to JMML-evolved AML. PMID:28007021
Co-occurrence and mutual exclusivity
- Co-occurred with PTPN11 D61Y in one pediatric JMML/AML case; the combination is characteristic of RAS-pathway-driven myeloid neoplasia. PMID:28007021
Therapeutic relevance
- No direct targeted therapy for SETBP1 mutations is described in the corpus; MEK inhibitors may be relevant given the RAS-pathway context. PMID:28007021
Open questions
- The prognostic impact of SETBP1 mutations in pediatric AML versus JMML requires larger cohort validation. PMID:28007021
Sources
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