ArticleClinical and translational medicine2023
Identification of IKZF1 genetic mutations as new molecular subtypes in acute myeloid leukaemia.
Article in Clinical and translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- IKZF1Leukemia · 2026Article
- A novel human acute myeloid leukemia cell line SDEY-AML1 with KMT2A: MLLT3, IKZF1: EVX1 fusions exhibits high tumorigenicity in NSG mice.Scientific reports · 2026Article
- CDK4/6 inhibition overcomes venetoclax resistance mechanisms with enhanced combination activity in acute myeloid leukemia.Cell reports. Medicine · 2026Article
- Review
- The role of IKZF1 rs4132601 and Δ4-7 somatic deletion in acute lymphoblastic leukemia: a bioinformatics and case-control study.Molecular biology reports · 2025Article
- The IKZF1 N159S mutation is associated with poor outcome and a distinct molecular profile in adult patients with AML.British journal of haematology · 2025Article
- The E3 ubiquitin ligase Herc1 modulates the response to nucleoside analogs in acute myeloid leukemia.Blood advances · 2024Article
- Multifaceted roles ofFrontiers in oncology · 2024Review
- Article
- Identification of IKZF1 genetic mutations as new molecular subtypes in acute myeloid leukaemia.Clinical and translational medicine · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic mutations of IKZF1 have been frequently delineated in B-lineage acute leukaemia (B-ALL) but rarely elucidated in acute myeloid leukaemia (AML). IKZF1 mutations confer a poor prognosis in AML, and hotspot mutations of IKZF1, N159Y and N159S tend to occur in B-ALL and AML respectively. However, the pathogenesis of IKZF1 N159S in AML and IKZF1 lineage susceptibility are largely unknown.
methodsThe genetic and clinical characteristics of IKZF1-mutated AML patients were evaluated. Multi-omics analysis and functional assays were performed in vitro using IKZF1 mutations knock-in AML cell lines.
results23 (4.84%) small sequence variants of IKZF1 were identified in 475 newly diagnosed AML (non-M3) patients. Based on RNA sequencing, three classes of IKZF1-related AML were defined, including 9 patients (39.13%) with IKZF1 N159S mutations, 10 (43.47%) with CEBPA mutations and 4 others (17.39%). IKZF1 N159S may define a unique subgroup with higher HOXA/B expression and native B-cell immune fractions. Gene expression data of multiple knock-in cell lines indicate that the lymphocyte differentiation-related MME and CD44 kept high expression in IKZF1 N159Y but were downregulated in N159S. CUT&TAG sequencing showed that IKZF1 N159S reshaped the binding profiles of IKZF1. Integration analysis suggested that the pathogenesis of IKZF1 N159S may depend on the deregulation of several cofactors, such as oncogenic MYC and CPNE7 targets.
conclusionsCollectively, we dissected the molecular spectrum and clinical features of IKZF1-related AML, which may promote an in-depth understanding of the pathogenesis, lineage susceptibility and clinical research of AML.
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