{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:03:39Z","timestamp":1779696219467,"version":"3.53.1"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute leukaemia is a highly aggressive malignancy with significant unmet therapeutic needs, partly due to epigenetic dysregulation. Here, we uncover deoxynucleotidyl transferase terminal\u2010interacting protein 1 (DNTTIP1) within the mitotic deacetylase complex (MiDAC) as a previously unrecognised epigenetic regulator crucial for leukaemic cell survival and elucidate its mechanistic and translational significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using cellular, biochemical, and genetic perturbations, coupled with validation in multiple in vivo leukaemia mouse models, we characterised DNTTIP1's role in acute leukaemia. An integrated multi\u2010omics analysis incorporating RNA\u2010seq, cleavage under targets and tagmentation (CUT&amp;Tag) and assay for transposase\u2010accessible chromatin using sequencing (ATAC\u2010seq) revealed that DNTTIP1 recruits histone deacetylase 1\/2 (HDAC1\/2) to silence BCL2\u2010modifying factor (BMF) and drive leukaemogenesis, validated by chromatin immunoprecipitation quantitative PCR (ChIP\u2010qPCR). Drug synergy assays identify poly(ADP\u2010ribose) polymerase (PARP)\/HDAC\/BCL2 inhibitor combinatorial efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>DNTTIP1 depletion impaired MiDAC recruitment in acute leukaemia, leading to histone H3 lysine 27 (H3K27) hyperacetylation at the BMF promoter and reactivating this effector. Upregulated BMF disrupted BCL2\u2010mediated survival, triggering coordinated autophagy and apoptosis. Combined HDAC1\/2 and BCL2 inhibition exerts synergistic anti\u2010leukaemic effects, a therapeutic strategy currently under clinical evaluation. Further, PARP inhibition profoundly enhanced this synergy by impairing DNA damage repair, unveiling a novel triple\u2010combination strategy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our work defines the DNTTIP1\u2012HDAC1\/2\u2012BMF axis as a pivotal epigenetic vulnerability in acute leukaemia and provides preclinical rationale for targeting this axis. These findings offer a validated biological framework for advancing this targeted combination therapy into clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>DNTTIP1 is overexpressed in acute leukaemia and associated with poor prognosis.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>DNTTIP1 acts as a scaffold for the MiDAC complex, recruiting HDAC1\/2 to silence BMF and inhibit leukaemic cell death.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Pharmacological disruption of the DNTTIP1\u2013HDAC1\/2\u2013BMF axis impairs leukaemogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70603","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:41:56Z","timestamp":1769593316000},"source":"Crossref","is-referenced-by-count":0,"title":["DNTTIP1 drives leukaemogenesis through MiDAC\u2010mediated epigenetic silencing of BMF"],"prefix":"10.1002","volume":"16","author":[{"given":"Ruolin","family":"Xiu","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine Department of Hematology NHC Key Laboratory of Cell Transplantation Key Laboratory of Hepatosplenic Surgery of Ministry of Education, The First Affiliated Hospital of Harbin Medical University Harbin China"},{"name":"Department of Hematology The First Affiliated Hospital of Harbin Medical University  Harbin 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