{"entity": "publication", "iuid": "accfc620123a4f83a114c85f6b6d879a", "timestamp": "2026-08-22T06:56:28.989Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/accfc620123a4f83a114c85f6b6d879a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/accfc620123a4f83a114c85f6b6d879a"}}, "title": "Inhibition of Oxidized Nucleotide Sanitation By TH1579 and Conventional Chemotherapy Cooperatively Enhance Oxidative DNA Damage and Survival in AML.", "authors": [{"family": "Centio", "given": "Anders", "initials": "A", "orcid": "0000-0002-9449-8123", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/06fa3c40ce4e42d08a2decc2c31fb999.json"}}, {"family": "Estruch", "given": "Montserrat", "initials": "M", "orcid": "0000-0002-7162-4158", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0e189e53cbfa47948171e1ae2e333f20.json"}}, {"family": "Reckzeh", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6391-625X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8be435d384a94651b2c4bb755a42635e.json"}}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Vittori", "given": "Camilla", "initials": "C", "orcid": "0000-0001-9441-8982", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fc343c36814461891e49adc308c0d7a.json"}}, {"family": "Engelhard", "given": "Sophia", "initials": "S", "orcid": "0000-0003-1583-1010", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b0a2461ac33742e5a14fec68c4219522.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8b6cab92fb2c4597a0c04777095f80db.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Theilgaard-M\u00f6nch", "given": "Kim", "initials": "K", "orcid": "0000-0002-4239-4939", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/622932c3f158460b845d61ce15ca7345.json"}}], "type": "journal article", "published": "2022-05-04", "journal": {"title": "Mol. Cancer Ther.", "issn": "1538-8514", "volume": "21", "issue": "5", "pages": "703-714", "issn-l": "1535-7163"}, "abstract": "Currently, the majority of patients with acute myeloid leukemia (AML) still die of their disease due to primary resistance or relapse toward conventional reactive oxygen species (ROS)- and DNA damage-inducing chemotherapy regimens. Herein, we explored the therapeutic potential to enhance chemotherapy response in AML, by targeting the ROS scavenger enzyme MutT homolog 1 (MTH1, NUDT1), which protects cellular integrity through prevention of fatal chemotherapy-induced oxidative DNA damage. We demonstrate that MTH1 is a potential druggable target expressed by the majority of patients with AML and the inv(16)/KITD816Y AML mouse model mimicking the genetics of patients with AML exhibiting poor response to standard chemotherapy (i.e., anthracycline & cytarabine). Strikingly, combinatorial treatment of inv(16)/KITD816Y AML cells with the MTH1 inhibitor TH1579 and ROS- and DNA damage-inducing standard chemotherapy induced growth arrest and incorporated oxidized nucleotides into DNA leading to significantly increased DNA damage. Consistently, TH1579 and chemotherapy synergistically inhibited growth of clonogenic inv(16)/KITD816Y AML cells without substantially inhibiting normal clonogenic bone marrow cells. In addition, combinatorial treatment of inv(16)/KITD816Y AML mice with TH1579 and chemotherapy significantly reduced AML burden and prolonged survival compared with untreated or single treated mice. In conclusion, our study provides a rationale for future clinical studies combining standard AML chemotherapy with TH1579 to boost standard chemotherapy response in patients with AML. Moreover, other cancer entities treated with ROS- and DNA damage-inducing chemo- or radiotherapies might benefit therapeutically from complementary treatment with TH1579.", "doi": "10.1158/1535-7163.MCT-21-0185", "pmid": "35247918", "labels": [], "xrefs": [{"db": "pii", "key": "681955"}], "notes": [], "created": "2026-08-21T12:29:45.130Z", "modified": "2026-08-21T12:29:45.235Z"}