{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:21:59Z","timestamp":1780633319173,"version":"3.54.1"},"reference-count":31,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,10,21]]},"abstract":"<jats:p>Differentiation arrest is a hallmark of acute leukemia. Genomic alterations in B cell differentiation factors such as PAX5, IKZF1, and EBF-1 have been identified in more than half of all cases of childhood B precursor acute lymphoblastic leukemia (ALL). Here, we describe a perturbed epigenetic and transcriptional regulation of ZNF423 in ALL as a novel mechanism interfering with B cell differentiation. Hypomethylation of ZNF423 regulatory sequences and BMP2 signaling result in transactivation of ZNF423\u03b1 and a novel ZNF423\u03b2-isoform encoding a nucleosome remodeling and histone deacetylase complex\u2013interacting domain. Aberrant ZNF423 inhibits the transactivation of EBF-1 target genes and leads to B cell maturation arrest in vivo. Importantly, ZNF423 expression is associated with poor outcome of ETV6-RUNX1\u2013negative B precursor ALL patients. Our work demonstrates that ALL is more than a genetic disease and that epigenetics may uncover novel mechanisms of disease with prognostic implications.<\/jats:p>","DOI":"10.1084\/jem.20130497","type":"journal-article","created":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T07:57:49Z","timestamp":1380614269000},"page":"2289-2304","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":39,"title":["Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of <i>ETV6-RUNX1<\/i> negative B precursor acute lymphoblastic leukemia"],"prefix":"10.1084","volume":"210","author":[{"given":"Lena","family":"Harder","sequence":"first","affiliation":[{"name":"Research Institute Children\u2019s Cancer Center and Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 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