IKZF1

Overview

IKZF1 (IKAROS Family Zinc Finger 1, also known as Ikaros) encodes a zinc-finger transcription factor essential for lymphoid development and differentiation. Deletions and loss-of-function mutations in IKZF1 are a hallmark of high-risk B-cell ALL, particularly Ph-like ALL. In contrast to other high-risk ALL subtypes, IKZF1 alterations are infrequent in hypodiploid ALL.

Alterations observed in the corpus

  • Infrequent in hypodiploid ALL (both near haploid and low hypodiploid subtypes), in contrast to its established role as a key driver in non-hypodiploid high-risk B-ALL; this pattern was noted in a WGS/WES study of 44 pediatric ALL tumors (St. Jude cohort) PMID:23334668
  • Co-amplified with EGFR and ETV1 at chr 7p in a metastasis-private high-level amplification event in metastatic CRC PMID:25164765
  • Altered in 36.7% of DUX4/ERG B-ALL cases (1,913-patient cohort); notably, IKZF1 alterations were NOT associated with poor outcome in this subtype, in contrast to other B-ALL subtypes where IKZF1 loss is an adverse marker — findings directly impact risk stratification. PMID:27776115
  • Identified as novel recurrently mutated gene in metastatic colorectal cancer (MSS subgroup) by a 1,211-patient WES/WGS/transcriptome study PMID:29316426

Cancer types (linked)

  • BLL (B-lymphoblastic leukemia): IKZF1 deletions are infrequent in hypodiploid ALL subtypes, distinguishing these from Ph-like and other high-risk B-ALL where IKZF1 loss is prominent PMID:23334668

Co-occurrence and mutual exclusivity

  • Mutually absent with the hypodiploid ALL genetic profile (NF1, IKZF2, IKZF3 alterations); low frequency contrasts with high frequency in Ph-like ALL PMID:23334668

Therapeutic relevance

  • IKZF1 loss in B-ALL has been associated with glucocorticoid resistance; PI3K/mTOR inhibitors are active in hypodiploid ALL subtypes where IKZF1 is intact PMID:23334668

Open questions

  • Mechanistic basis for why hypodiploid ALL tolerates loss of IKZF1 alterations compared to other high-risk B-ALL subtypes is unresolved PMID:23334668

Sources

This page was processed by entity-page-writer on 2026-05-06. - PMID:25164765

This page was processed by wiki-cli on 2026-05-11. - PMID:27776115

This page was processed by entity-page-writer on 2026-05-15. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15.