ArticleBlood2021
Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study.Frontiers in immunology · 2021Pooled it
- Abnormal SCID Newborn Screening and Spontaneous Recovery Associated with a Novel Haploinsufficiency IKZF1 Mutation.Journal of clinical immunology · 2021Trial
- Autoimmune Cytopenias and Dysregulated Immunophenotype Act as Warning Signs of Inborn Errors of Immunity: Results From a Prospective Study.Frontiers in immunology · 2021Trial
- Article
- Systematic functional validation of IKAROS variants from patients and laboratory-generated mutations.Blood advances · 2026Article
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study.Frontiers in immunology · 2026Article
- Article
- IKZF-associated inborn errors of immunity.Journal of human immunity · 2025Review
- IKAROS protein stability is regulated by its early N-terminal region and C-terminal dimerization domain.Clinical immunology (Orlando, Fla.) · 2025Article
- Review
- Helios-Illuminating the way for lymphocyte self-control.Immunology · 2025Review
- IKAROS: from chromatin organization to transcriptional elongation control.Cell death and differentiation · 2025Review
- Advances in epigenetic therapies for B-cell non-hodgkin lymphoma.Annals of hematology · 2024Review
- A mutant BCL11B-N440K protein interferes with BCL11A function during T lymphocyte and neuronal development.Nature immunology · 2024Article
- Myeloid sarcoma with plasmacytoid dendritic cell-like proliferation associated with IKZF1, ETV6 and DNMT3A mutations.International journal of hematology · 2024Article
- IKZF1 and UBR4 gene variants drive autoimmunity and Th2 polarization in IgG4-related disease.The Journal of clinical investigation · 2024Article
- AIOLOS-Associated Inborn Errors of Immunity.Journal of clinical immunology · 2024Review
- IKAROS gain of function disease: Allogeneic hematopoietic cell transplantation experience and expanded clinical phenotypes.Clinical immunology (Orlando, Fla.) · 2024Article
- Disease-associated AIOLOS variants lead to immune deficiency/dysregulation by haploinsufficiency and redefine AIOLOS functional domains.The Journal of clinical investigation · 2024Article
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 4 countries.
Funding
Abstract
IKAROS is a transcription factor forming homo- and heterodimers and regulating lymphocyte development and function. Germline mutations affecting the IKAROS N-terminal DNA binding domain, acting in a haploinsufficient or dominant-negative manner, cause immunodeficiency. Herein, we describe 4 germline heterozygous IKAROS variants affecting its C-terminal dimerization domain, via haploinsufficiency, in 4 unrelated families. Index patients presented with hematologic disease consisting of cytopenias (thrombocytopenia, anemia, neutropenia)/Evans syndrome and malignancies (T-cell acute lymphoblastic leukemia, Burkitt lymphoma). These dimerization defective mutants disrupt homo- and heterodimerization in a complete or partial manner, but they do not affect the wild-type allele function. Moreover, they alter key mechanisms of IKAROS gene regulation, including sumoylation, protein stability, and the recruitment of the nucleosome remodeling and deacetylase complex; none affected in N-terminal DNA binding defects. These C-terminal dimerization mutations are largely associated with hematologic disorders, display dimerization haploinsufficiency and incomplete clinical penetrance, and differ from previously reported allelic variants in their mechanism of action. Dimerization mutants contribute to the growing spectrum of IKAROS-associated diseases displaying a genotype-phenotype correlation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.