{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:46:52Z","timestamp":1770990412141,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24ama221131h"],"award-info":[{"award-number":["JP24ama221131h"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    CALM (Clathrin Assembly Lymphoid Myeloid Leukemia)\u2010AF10, a fusion gene commonly associated with acute myeloid leukemia (AML), arises from the\n                    <jats:italic>t<\/jats:italic>\n                    (10;11) translocation and is linked to poor prognosis. In this study, we demonstrate that the CCCTC\u2010binding factor (CTCF) plays a critical role in both the initiation and maintenance of CALM\u2010AF10\u2010induced AML (CALM\u2010AF10 AML). In\u00a0vivo, CTCF deficiency significantly extended the survival of CALM\u2010AF10 AML mice. In\u00a0vitro,\n                    <jats:italic>CTCF<\/jats:italic>\n                    knockout (KO) reduced the colony\u2010forming capacity of CALM\u2010AF10 AML cells and induced their differentiation into macrophage\u2010like cells. RNA sequencing (RNA\u2010seq) of\n                    <jats:italic>CTCF<\/jats:italic>\n                    KO cells revealed that\n                    <jats:italic>Transglutaminase 2<\/jats:italic>\n                    (\n                    <jats:italic>TGM2<\/jats:italic>\n                    ) was the most significantly downregulated gene. Chromatin immunoprecipitation sequencing (ChIP\u2010seq) analysis indicated increased repressive histone mark, H3K27 trimethylation (H3K27me3), accompanied by reduced active histone marks, including H3K4 trimethylation (H3K4me3) and H3K27 acetylation (H3K27ac), at the transcription start site (TSS) of\n                    <jats:italic>Tgm2<\/jats:italic>\n                    following\n                    <jats:italic>CTCF<\/jats:italic>\n                    KO. Knockdown of\n                    <jats:italic>Tgm2<\/jats:italic>\n                    using short hairpin RNA (shRNA) in CALM\u2010AF10 AML cells and in the human leukemic cell line U937 harboring the CALM\u2010AF10 fusion gene resulted in reduced colony formation and proliferation. This also promoted differentiation into macrophage\u2010like cells, recapitulating the effects observed with\n                    <jats:italic>CTCF<\/jats:italic>\n                    KO. Similarly, comparable outcomes were observed with GK921, a TGM2 inhibitor, highlighting the impact of TGM2 blockade. These findings suggest that CTCF regulates\n                    <jats:italic>TGM2<\/jats:italic>\n                    expression by modulating post translational modifications of histones at its TSS, thereby preserving the undifferentiated state of CALM\u2010AF10 AML cells. The demonstrated efficacy of TGM2 inhibitors further underscores the importance of TGM2 in this subtype of leukemia.\n                  <\/jats:p>","DOI":"10.1111\/cas.70161","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T16:40:46Z","timestamp":1756399246000},"page":"3016-3026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CTCF<\/scp>\n                    Is Essential for the Development and Maintenance of\n                    <scp>CALM<\/scp>\n                    \u2010\n                    <scp>AF10<\/scp>\n                    \u2010Induced Leukemia"],"prefix":"10.1111","volume":"116","author":[{"given":"Yoko","family":"Kuroki","sequence":"first","affiliation":[{"name":"Center for Translational Research Fujita Health University  Aichi Japan"},{"name":"Division of Hematological Malignancy National Cancer Center Research Institute  Tokyo Japan"},{"name":"Course of Advanced Clinical Research of Cancer Juntendo University Graduate School of Medicine  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazutsune","family":"Yamagata","sequence":"additional","affiliation":[{"name":"Division of Hematological Malignancy National Cancer Center Research Institute  Tokyo Japan"},{"name":"Department of Biochemistry Fujita Health University  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Aikawa","sequence":"additional","affiliation":[{"name":"Division of Hematological Malignancy National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutaka","family":"Shima","sequence":"additional","affiliation":[{"name":"Center for Translational Research Fujita Health University  Aichi Japan"},{"name":"Division of Hematological Malignancy National Cancer Center Research Institute  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisafumi","family":"Shioneri","sequence":"additional","affiliation":[{"name":"Center for Translational Research Fujita Health University  Aichi Japan"},{"name":"Oncology Innovation Center Fujita Health University  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-0407","authenticated-orcid":false,"given":"Issay","family":"Kitabayashi","sequence":"additional","affiliation":[{"name":"Center for Translational Research Fujita Health University  Aichi Japan"},{"name":"Division of Hematological Malignancy National Cancer Center Research Institute  Tokyo Japan"},{"name":"Course of Advanced Clinical Research of Cancer Juntendo University Graduate School of Medicine  Tokyo Japan"},{"name":"Oncology Innovation Center Fujita Health University  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0178"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022009010"},{"key":"e_1_2_11_4_1","first-page":"4662","article-title":"MLL and CALM Are Fused to AF10 in Morphologically Distinct Subsets of Acute Leukemia With Translocation t(10;11): Both Rearrangements Are Associated With a Poor Prognosis","volume":"91","author":"Dreyling M. 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