{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:35:05Z","timestamp":1785857705616,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti\u2010tumor effects have previously been demonstrated for GSK\u2010J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To characterize the effect of GSK\u2010J4, drug response profiling, CRISPR\u2010Dropout Screening, BH3 profiling and immunoblotting were carried out in ALL cell lines or patient derived samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here we provide evidence that GSK\u2010J4 downregulates cyclic AMP\u2010responsive element\u2010binding protein (CREB) and CREBBP in B\u2010cell precursor\u2010ALL cell lines and patient samples. High CREBBP expression in BCP\u2010ALL cell lines correlated with high GSK\u2010J4 sensitivity and low dexamethasone sensitivity. GSK\u2010J4 treatment also induced Bcl\u20102 and Bcl\u2010XL dependency and apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study proposes H3K27 demethylase inhibition as a potential treatment strategy for patients with treatment\u2010resistant ALL, using CREBBP as a biomarker for drug response and combining GSK\u2010J4 with venetoclax and navitoclax as synergistic partners.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.70596","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T07:46:38Z","timestamp":1736495198000},"page":"1-7","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibiting\n                    <scp>H3K27<\/scp>\n                    Demethylases Downregulates\n                    <scp>CREB<\/scp>\n                    \u2010\n                    <scp>CREBBP<\/scp>\n                    , Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2324-7159","authenticated-orcid":false,"given":"Juan","family":"Lazaro\u2010Navarro","sequence":"first","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Alcon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Barcelona Spain"},{"name":"Networking Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine (CIBER\u2010BBN)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathurin","family":"Dorel","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Alasfar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenz","family":"Bastian","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology\/Oncology University Medical Center Schleswig\u2010Holstein  Campus Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Baldus","sequence":"additional","affiliation":[{"name":"Medical Department II, Hematology\/Oncology University Medical Center Schleswig\u2010Holstein  Campus Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Astrahantseff","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Laure","family":"Yaspo","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Montero","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia","family":"Eckert","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology\/Hematology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"German Cancer Consortium (DKTK) German Cancer Research Center (DKFZ)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.1636"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4469"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019002220"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09727"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032\u2010020\u201001395\u20105"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15041219"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201012\u20101511"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4177"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.695225"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004513"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432\u2010018\u20102631\u20107"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2017.08.024"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/JMCB\/MJZ032"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.144964"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201029224\u20105"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00799"},{"key":"e_1_2_10_18_1","first-page":"1","article-title":"Venetoclax 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