{"id":9634,"date":"2026-03-26T22:00:36","date_gmt":"2026-03-26T13:00:36","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/eng\/?page_id=9634"},"modified":"2026-03-27T13:25:11","modified_gmt":"2026-03-27T04:25:11","slug":"inoue2026-3-26","status":"publish","type":"page","link":"https:\/\/www.med.osaka-u.ac.jp\/eng\/activities\/results\/2026year\/inoue2026-3-26","title":{"rendered":"Koutarou Nishimura,  Daichi Inoue \u226aCancer Pathology\u226b <span>Comprehensive Molecular and Functional Analysis of NUTM1-Rearranged Leukemia<\/span>"},"content":{"rendered":"<ul class=\"linkBar clearfix\">\n<li><a href=\"https:\/\/www.med.osaka-u.ac.jp\/activities\/results\/2026year\/inoue2026-4-1\">Text in Japanese<\/a><\/li>\n<\/ul>\n<p><em><i>Blood<\/i><\/em><\/p>\n<p>Researchers in Japan find that B-cell acute lymphoblastic leukemia with NUTM1 gene rearrangements is a unique form of the disease, with a distinct pattern of gene activity and gene regulation that is highly sensitive to chemotherapy<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-9637 size-large\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/f4848aecdd82aaf8d8c472c8911205e9-1024x471.jpg?_t=1773621347\" alt=\"\" width=\"900\" height=\"414\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/f4848aecdd82aaf8d8c472c8911205e9-1024x471.jpg 1024w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/f4848aecdd82aaf8d8c472c8911205e9-400x184.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/f4848aecdd82aaf8d8c472c8911205e9-768x354.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/f4848aecdd82aaf8d8c472c8911205e9.jpg 1299w\" sizes=\"(max-width: 900px) 100vw, 900px\" \/><br \/>Fig1:Comprehensive analysis of <em>NUTM1<\/em> rearranged infant leukemia (Created with BioRender.com)<br \/>Credit: Koutarou Nishimura<\/p>\n<p>Osaka, Japan \u2013 Despite a host of checks and balances that usually prevent harmful genetic mutations, sometimes mistakes happen, with serious consequences. Now, researchers from Japan elucidate how a common mutation underlying a common childhood cancer also makes it highly treatable.<\/p>\n<p>In a study published in March in Blood, researchers from The University of Osaka, Institute of Science Tokyo, and The University of Tokyo revealed that infant B-cell acute lymphoblastic leukemia (B-ALL) caused by NUTM1 gene rearrangements is distinct from other forms of B-ALL and responds better to treatment.<br \/>Genomic rearrangements, which happen when genes are \u201ccut and pasted\u201d into the wrong locations, resulting in the production of abnormal proteins, are the cause of many cancers. The NUTM1 gene is rearranged in a large percentage of infant B-ALL cases, and it is especially common for this to result in fusion with the BRD9 gene, which encodes a bromodomain protein.<br \/>\u201cBromodomain family proteins are frequently implicated in cancers that involve NUTM1 rearrangement,\u201d says co-first author of the study Koutarou Nishimura. \u201cHowever, it was unclear how the BRD9-NUTM1 fusion leads to the development of infant B-ALL.\u201d<br \/>To address this, the researchers performed comprehensive analyses of genomic and clinical data from patients with B-ALL. In addition, they investigated the effects of the BRD9-NUTM1 fusion in mice and in precursor cell lines that develop into blood cells.<br \/>\u201cThe results were very striking,\u201d explains Daichi Inoue, corresponding author. \u201cWe found that, unlike other forms of B-ALL caused by different mutations, those with NUTM1 rearrangements shown a unique pattern of gene activity and gene regulation, especially decreased DNA methylation\u2014a chemical tag that helps control how genes are turned on and off\u2014throughout the genome.\u201d<br \/>Furthermore, the researcher team found that NUTM1 fusion genes drive leukemia development by triggering B-cell differentiation (i.e. the maturation of immune cells into B cells) and increasing the lifespan of blood cells. Importantly, leukemias with the BRD9-NUTM1 fusion were extremely sensitive to chemotherapy, in contrast to leukemias with other common gene rearrangements.<br \/>\u201cOur study shows that leukemias with NUTM1 rearrangements have unique molecular profiles that make them vulnerable to treatment and are associated with improved clinical outcomes,\u201d says Nishimura.<br \/>The findings from this study will help optimize treatment for infants with this type of B-ALL, as they are likely to respond to lower treatment intensities. Exploring the functional effects of the protein encoded by the BRD9-NUTM1 fusion could also help identify additional treatment targets in the future.<\/p>\n<p>###<\/p>\n<p>The article, \u201cComprehensive Molecular and Functional Analysis of NUTM1-Rearranged Leukemia,\u201d will be published in <em>Blood<\/em> at DOI: <a href=\"https:\/\/doi.org\/10.1182\/blood.2024026928\">https:\/\/doi.org\/10.1182\/blood.2024026928<\/a><\/p>\n<p><strong>Summary: <\/strong>Researchers from The University of Osaka found that leukemia caused by <em>NUTM1 <\/em>rearrangements is distinguished from other forms of B-cell acute lymphoblastic leukemia (B-ALL) by a unique pattern of gene activity and gene regulation. Unlike the common form of B-ALL caused by <em>KMT2A<\/em> rearrangement, which is resistant to treatment, leukemic cells with <em>NUTM1<\/em> rearrangements are highly sensitivity to chemotherapy.<\/p>\n<p><strong>Tweet:<\/strong> An unusual arrangement? <em>NUTM1<\/em>-rearranged B-ALL exhibits global hypomethylation and is highly sensitive to chemotherapy<br \/>@UOsaka_en<\/p>\n<p><strong>Primary Keyword: <\/strong>Diseases and disorders<\/p>\n<p><strong>Additional Keyword:<\/strong><strong>\u00a0<\/strong>Leukemia, Lymphocytes, B lymphocytes, Oncology, Cancer genetics, Medical genetics, Chemotherapy<\/p>\n<p><strong>Method of Research:<\/strong>Experimental study<\/p>\n<p><strong>Subject of Research:<\/strong> Animals<\/p>\n<p>&nbsp;<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-9638 size-large\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/efce9403efaf6cce2d853aa8430f0f11-1024x496.jpg?_t=1773621514\" alt=\"\" width=\"900\" height=\"436\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/efce9403efaf6cce2d853aa8430f0f11-1024x496.jpg 1024w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/efce9403efaf6cce2d853aa8430f0f11-400x194.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/efce9403efaf6cce2d853aa8430f0f11-768x372.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/efce9403efaf6cce2d853aa8430f0f11.jpg 1299w\" sizes=\"(max-width: 900px) 100vw, 900px\" \/><br \/>Figure 2\uff1a <em>NUTM1 <\/em>rearrangement drives leukemogenesis\uff08Created with BioRender.com)<br \/>Credit: Koutarou Nishimura<\/p>\n<p class=\"figure\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-9636 size-large\" src=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/6cc0d0ca7020b65b6563a91ae31ad522-1024x469.jpg?_t=1773621514\" alt=\"\" width=\"900\" height=\"412\" srcset=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/6cc0d0ca7020b65b6563a91ae31ad522-1024x469.jpg 1024w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/6cc0d0ca7020b65b6563a91ae31ad522-400x183.jpg 400w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/6cc0d0ca7020b65b6563a91ae31ad522-768x352.jpg 768w, https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-content\/uploads\/2026\/03\/6cc0d0ca7020b65b6563a91ae31ad522.jpg 1299w\" sizes=\"(max-width: 900px) 100vw, 900px\" \/><br \/>Figure 3\uff1a <em>NUTM1<\/em>-rearranged leukemia is\u00a0highly responsive\u00a0to conventional therapy\uff08Created with BioRender.com)<br \/>Credit: Koutarou Nishimura<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Title\uff1a<\/strong>\u201cComprehensive Molecular and Functional Analysis of NUTM1-Rearranged Leukemia\u201d<\/p>\n<p><strong>Journal\uff1a<\/strong><em>Blood<\/em><\/p>\n<p><strong>Authors\uff1a<\/strong>Koutarou Nishimura<sup>\uff0a<\/sup>, Tomoya Isobe<sup>\uff0a<\/sup>, Weijia Zang, Muran Xiao, Masaki Nomura, Yui Koike, Tsukasa Shigehiro, Akira Nishimura, Aiko Sato-Otsubo, Hiromi Yamazaki, Hiromi Ito, Wataru Saika, Yifan Zhang, Yumi Aoyama, Chihiro Hasegawa, Takaya Yamasaki, Yasuo Kubota, Kentaro Ohki, Nobutaka Kiyokawa, Genta Nagae, Kenichi Yoshida, Yasuhito Nannya, Hiroo Ueno, Shiro Fukuda, Kenji Tatsuno, Shuichi Tsutsumi, Yusuke Shiozawa, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Mariko Eguchi, Yuki Arakawa, Katsuyoshi Koh, Daisuke Tomizawa, Takako Miyamura, Eiichi Ishii, Shuki Mizutani, Satoru Miyano, Hiroyuki Aburatani, Seishi Ogawa, Akifumi Takaori-Kondo, Akihiko Yokoyama, Omar Abdel-Wahab, Junko Takita, Tomokatsu Ikawa, Masatoshi Takagi<sup>\u2020<\/sup>, Daichi Inoue<sup>\u2020<\/sup>\u3000\uff0aContributed equally, <sup>\u2020<\/sup>Corresponding author<\/p>\n<p><strong>DOI\uff1a<\/strong><a href=\"https:\/\/doi.org\/10.1182\/blood.2024026928\">10.1182\/blood.2024026928<\/a><\/p>\n<p><strong>Funded by\uff1a<br \/><\/strong>Japan Society for the Promotion of Science<br \/>Japan Agency for Medical Research and Development<br \/>Japan Science and Technology Agency<br \/>the American Society of Hematology<br \/>Japanese Society of Hematology<br \/>Leukemia &amp; Lymphoma Society<br \/>National Cancer Institute<br \/>National Institutes of Health<br \/>National Heart, Lung, and Blood Institute<br \/>the Edward P. Evans MDS Foundation<br \/>Senri Life Science Foundation<br \/>The Sumitomo Foundation<br \/>The Mitsubishi Foundation<br \/>KAKETSUKEN<br \/>Bristol Myers Squibb Foundation<br \/>Astellas Foundation for Research on Metabolic Disorders<br \/>Mochida Memorial Foundation for Medical and Pharmaceutical Research<br \/>Japan Leukemia Research Fund<br \/>Princess Takamatsu Cancer Research Fund<br \/>the Morgan Adams Foundation<br \/>The Naito Foundation<br \/>Takeda Science Foundation<br \/>Friends of Leukemia Research Fund<br \/>MSD Life Science Foundation<br \/>the Japan Foundation for Pediatric Research<br \/>the Funai Foundation for Information Technology<br \/>the Honjo International Scholarship Foundation<\/p>\n<p><strong>Article publication date\uff1a<\/strong>26-MAR-2026<\/p>\n<p><strong>Related links:<br \/><\/strong><\/p>\n<p>Cancer Pathology, The University of Osaka Graduate School of Medicine Faculty of Medicine<br \/><a href=\"https:\/\/www.med.osaka-u.ac.jp\/eng\/introduction\/research\/pathology\/cancer\">https:\/\/www.med.osaka-u.ac.jp\/eng\/introduction\/research\/pathology\/cancer<\/a><\/p>\n<p>Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe<br \/><a href=\"https:\/\/www.fbri-kobe.org\/english\/\">https:\/\/www.fbri-kobe.org\/english\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Text in Japanese Blood Researchers in Japan find that B-cell acute lymphoblastic leukemia with NUTM1 gene rear [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":9637,"parent":9667,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9634"}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/comments?post=9634"}],"version-history":[{"count":28,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9634\/revisions"}],"predecessor-version":[{"id":9680,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9634\/revisions\/9680"}],"up":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/pages\/9667"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media\/9637"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/eng\/wp-json\/wp\/v2\/media?parent=9634"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}