IKZF2
Overview
IKZF2 (IKAROS Family Zinc Finger 2, also known as Helios) is a zinc-finger transcription factor and member of the Ikaros family involved in lymphoid differentiation and Ras/PI3K pathway modulation. Deletions of IKZF2 are highly recurrent in low hypodiploid ALL and modulate RAS and PI3K signaling activity.
Alterations observed in the corpus
- Deletions in 52.9% of low hypodiploid ALL and 36.4% of adult low hypodiploid ALL (St. Jude WGS/WES, 44 pediatric ALL tumors); shRNA knockdown of IKZF2 increases pERK and pS6 levels, indicating a role as a Ras/PI3K pathway modulator PMID:23334668
- IKZF2 (Helios) is a transcription factor stabilizing regulatory T cell (Treg) suppressive function in NPC; IKZF2 degraders PLX-4545 and DKY709 are under clinical investigation to reprogram Tregs and restore anti-tumor immunity. PMID:24952746
Cancer types (linked)
- BLL (B-lymphoblastic leukemia, low hypodiploid): Deletions in ~53% of pediatric cases and ~36% of adult cases; functional data supports IKZF2 as a negative modulator of Ras/PI3K signaling in ALL PMID:23334668
Co-occurrence and mutual exclusivity
- Co-deleted with RB1 alterations in low hypodiploid ALL; found alongside TP53 mutations (which define this subtype) and IKZF3 deletions PMID:23334668
Therapeutic relevance
- IKZF2 loss upregulates PI3K/mTOR signaling; dual PI3K/mTOR inhibitors (BEZ235, GDC-0941) show activity in low hypodiploid ALL xenografts, suggesting IKZF2 loss contributes to therapeutic vulnerability PMID:23334668
Open questions
- Functional consequences of IKZF2 loss are based on shRNA knockdown in cell lines; in vivo validation in patient-derived models is needed PMID:23334668
Sources
This page was processed by entity-page-writer on 2026-05-11. - PMID:24952746
This page was processed by entity-page-writer on 2026-05-11.