{"id":150579,"date":"2025-08-16T13:21:15","date_gmt":"2025-08-16T13:21:15","guid":{"rendered":"https:\/\/www.europesays.com\/us\/150579\/"},"modified":"2025-08-16T13:21:15","modified_gmt":"2025-08-16T13:21:15","slug":"study-uncovers-molecular-switch-behind-chemoresistance-in-blood-cancer","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/150579\/","title":{"rendered":"Study uncovers molecular \u201cswitch\u201d behind chemoresistance in blood cancer"},"content":{"rendered":"

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Scientists at The Jackson Laboratory are studying new therapeutic targets for acute myeloid leukemia (AML), an aggressive hematological malignancy that accounts for 80% of acute leukemia cases in adults.\u00a0<\/p>\n

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Credit: The Jackson Laboratory<\/p>\n

One of the biggest challenges in cancer treatment is that certain cancers reappear after chemotherapy\u2014and an aggressive type of blood cancer called acute myeloid leukemia (AML) is notorious for this. Now, new research from The Jackson Laboratory (JAX) points to a previously unknown molecular mechanism behind that chemoresistance, and a way to potentially disarm it.<\/p>\n

In findings newly published in Blood Cancer Discovery<\/a>, a team led by JAX assistant professor Eric Wang<\/a> reports on the role of a protein called\u00a0RUNX1C in this mechanism. A little-known variation, or \u201cisoform\u201d of a gene called RUNX1, the RUNX1C protein helps regulate how blood cells resist chemotherapy.<\/p>\n

By studying data from AML patients from before they received chemotherapy and again after their cancer returned, the team found that in many cases a chemical tag known as\u00a0DNA methylation\u00a0had appeared in a section of the genome that normally controls the\u00a0RUNX1\u00a0gene. That small change flipped a genetic switch, forcing cancer cells to make more of the RUNX1C isoform, activating a mechanism that made them far better at withstanding chemotherapy.<\/p>\n

Specifically, RUNX1C turned on a gene called\u00a0BTG2. This interfered with the cells\u2019 RNA, slowing down cell activity and pushing leukemia cells into\u00a0a dormant or quiescent state where they stop dividing. In this state, cancer cells effectively hide from chemotherapy, which works best when cancer cells are actively dividing. In other words, dormant cancer cells go unnoticed and can \u201cwake up\u201d after treatment.<\/p>\n

\u201cThe problem right now is that there is no treatment for patients who relapse, and that\u2019s why our study is so important\u2014not just to understand what isoforms or genes mediate resistance but to understand how we can target them in the future,\u201d Wang said.\u00a0 \u201cScientists have done extensive RNA isoform analysis but not in the context of AML relapse. Our study is a good resource to show that in addition to genes, RNA isoforms are also very important in mediating chemoresistance.\u201d<\/p>\n

If a safe and targeted way can be developed to block RUNX1C in patients, it could prevent cancer cells from slipping into quiescence, making chemotherapy more effective and reducing the risk of relapse, Wang said. The team tested two RNA-targeting tools against RUNX1C in AML models both in cultured cells and in mice.<\/p>\n

Pairing RUNX1C inhibition with standard chemotherapy significantly improved the drugs\u2019 ability to kill leukemia cells. Without the isoform\u2019s influence, the dormant cancer cells \u201cwoke up\u201d and started dividing again\u2014precisely the state when chemotherapy is most effective.<\/p>\n

Dr. Cuijuan Han, the lead author of the study, explained, \u201cWe demonstrated that overexpressing this isoform confers resistance to many of the chemotherapy treatments used for AML. We\u2019ve done experiments to do the inverse, where we also knocked out the isoform and see that it confers sensitivity.\u201d<\/p>\n

Wang\u2019s lab is collaborating with other organizations to continue using these RNA-targeting tools, known as antisense oligonucleotides (ASOs), which can bind to RNA and block it from making certain proteins like RNA isoforms. If further studies confirm the results, targeting RUNX1C with ASO technology could become a powerful tool in the fight against AML, Wang said. While this technology is in experimental stages for rare neurological diseases at JAX, it hasn\u2019t been widely applied to AML or most other cancers.<\/p>\n

\u201cOur study provides a proof of principle that knocking down isoforms with the right technology could enhance or even overcome chemoresistance,\u201d Wang said. \u201cAlthough our lab does not focus on other cancers, applying this concept to other cancers may provide rationale to focus on whether targeting RNA isoforms can modulate drug response with different drugs and different cancers.\u201d<\/p>\n

Eric Wang was supported by The Jackson Laboratory Cancer Center (JAXCC) New Investigator Award (P30CA034196), JAX start-up funds, JAX Cancer Center Fast Forward Award, Leukemia Research Foundation (LRF), and Butler Family Foundation.\u00a0<\/p>\n

Journal<\/p>\n

Blood Cancer Discovery<\/p>\n

Method of Research<\/p>\n

Experimental study<\/p>\n

Subject of Research<\/p>\n

Animals<\/p>\n

Article Title<\/p>\n

An Isoform-Specific RUNX1C\u2013BTG2 Axis Governs AML Quiescence and Chemoresistance<\/p>\n

Article Publication Date<\/p>\n

11-Aug-2025<\/p>\n

Disclaimer:<\/strong> AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.<\/p>\n","protected":false},"excerpt":{"rendered":"image:\u00a0 Scientists at The Jackson Laboratory are studying new therapeutic targets for acute myeloid leukemia (AML), an aggressive…\n","protected":false},"author":3,"featured_media":150580,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[815,159,67,132,68],"class_list":{"0":"post-150579","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-united-states","11":"tag-unitedstates","12":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115038656318713332","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/150579","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=150579"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/150579\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/150580"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=150579"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=150579"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=150579"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}