IKZF3
Overview
IKZF3 (IKAROS Family Zinc Finger 3, also known as Aiolos) is a zinc-finger transcription factor in the Ikaros family involved in late B cell differentiation and Ras/PI3K pathway modulation. Deletions and frameshift mutations in IKZF3 are recurrent in near haploid ALL and upregulate ERK and S6 phosphorylation, implicating it as a modulator of RAS/PI3K signaling.
Alterations observed in the corpus
- Deletions and frameshift mutations in 13.2% of near haploid ALL (St. Jude WGS/WES, 44 pediatric ALL tumors); shRNA knockdown increases pERK and pS6, functionally linking IKZF3 loss to Ras/PI3K pathway activation PMID:23334668
- Recurrent L162R substitution in CLL (n=11, 2.0%; conservation 93/100); novel CLL driver with CCF rising in 3 of 4 relapse cases; key B-cell transcription factor; classified in chromatin modification driver group PMID:26466571
- IKZF3 identified as a fusion partner of ERBB2 in 4 samples; IKZF3 is a genomic neighbor of ERBB2, and fusions arise from local genomic instability potentially induced by HPV integration within 1 Mb of the ERBB2-IKZF3 locus in 3 of 4 cases. PMID:29617662
Cancer types (linked)
- BLL (B-lymphoblastic leukemia, near haploid): Deletions and frameshift mutations in 13.2% of near haploid ALL; functional data supports role as negative modulator of Ras/PI3K signaling PMID:23334668
Co-occurrence and mutual exclusivity
- Co-occurs with NF1 deletions, KRAS/NRAS activating mutations, and IKZF2 deletions in the near haploid ALL subtype PMID:23334668
Therapeutic relevance
- IKZF3 loss upregulates Ras/PI3K pathway activity; dual PI3K/mTOR inhibitors (BEZ235, GDC-0941) are active in near haploid ALL xenografts, suggesting IKZF3 loss contributes to PI3K pathway dependence PMID:23334668
Open questions
- Functional data on IKZF3 is based on shRNA knockdown in cell lines; in vivo validation and the mechanistic basis of PI3K pathway modulation by IKZF3 remain to be established PMID:23334668
Sources
This page was processed by entity-page-writer on 2026-05-06. - PMID:26466571
This page was processed by wiki-cli on 2026-05-14. - PMID:29617662
This page was processed by wiki-cli on 2026-05-15.