{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:55:52Z","timestamp":1790704552621,"version":"4.1.0"},"reference-count":41,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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.<\/jats:p>","DOI":"10.1182\/blood.2020007292","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T17:54:53Z","timestamp":1598464493000},"page":"349-363","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":56,"title":["Germline IKAROS dimerization haploinsufficiency causes hematologic cytopenias and malignancies"],"prefix":"10.1182","volume":"137","author":[{"given":"Hye Sun","family":"Kuehn","sequence":"first","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Niemela","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, Clinical Center, National 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