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Through integrative analysis of bulk and single-cell RNA sequencing data, we identified a conserved set of seven ZNF genes, including ZNF184, that are upregulated in acute lymphoblastic leukemia (ALL) and exhibit dynamic expression patterns linked to disease progression. Among these, ZNF184 uniquely localized to DNA double-strand breaks (DSBs) in a zinc finger domain-dependent manner. Functional analyses revealed that ZNF184 suppresses homologous recombination (HR)-mediated DNA repair by impeding BRCA1 recruitment, leading to accumulation of DNA damage. ZNF184 expression was elevated in primary ALL samples and associated with increased \u03b3H2AX levels and inferior overall survival in ALL patients. Loss of ZNF184 restored HR efficiency, reduced DNA damage burden, and enhanced genome stability, while re-expression re-sensitized cells to DNA-damaging agents. Mechanistically, ZNF184 directly interacted with TRIM28 and facilitated its recruitment to DSBs, modulating TRIM28 phosphorylation and chromatin remodeling through the HP1\/SUV39H1 complex. ZNF184 expression conferred heightened sensitivity to PARP inhibition and synergized with genotoxic chemotherapy in both cell lines and patient-derived ALL cells. These findings identify ZNF184 as a key modulator of DSB repair and a predictive biomarker for therapeutic strategies targeting HR-deficient ALL.<\/jats:p>","DOI":"10.1093\/nar\/gkag486","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T11:19:30Z","timestamp":1777893570000},"source":"Crossref","is-referenced-by-count":1,"title":["ZNF184 negatively regulates HR repair and predicts poor prognosis in acute lymphoblastic leukemia"],"prefix":"10.1093","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9069-4576","authenticated-orcid":false,"given":"Won Chan","family":"Hwang","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Ulsan National Institute of Science and Technology , Ulsan 44919 ,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Young","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Samsung Medical Center, 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