BCL11B enhancer hijacking by t(14;16)(q32;q24) translocation defines a novel high-risk subtype of T-ALL - PubMed
3 days ago
- #prognosis
- #enhancer hijacking
- #T-ALL
- BCL11B enhancer hijacking by t(14;16)(q32;q24) translocation defines a novel high-risk subtype of T-ALL.
- Integrated analysis of pediatric and adult T-ALL and MPALs identified 14 patients with t(14;16)(q32;q24) translocation, GATA3 mutations, and CDKN2A/B deletions.
- The translocation causes ectopic overexpression of FENDRR, FOXF1, and FOXC2, activating EMT transcription signatures.
- Immunophenotypic and single-cell RNA-seq analyses revealed lineage ambiguity with myeloid and B-cell differentiation potentials.
- FOXF1 overexpression promotes myeloid differentiation while suppressing T-cell differentiation in CD34-positive cord blood cells.
- This subtype is detected in 0.15-4.0% of T-ALL/MPAL cases, with a median age of 15 years and enrichment in adolescents and young adults (AYA).
- Patients with t(14;16)(q32;q24) have an extremely poor prognosis, worse than other high-risk T-ALL groups.
- The findings highlight the need for novel subtype-specific therapeutic approaches.