{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:10:08Z","timestamp":1780049408253,"version":"3.53.1"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the practical development projects by Fukushima prefecture","award":["1142"],"award-info":[{"award-number":["1142"]}]},{"name":"a grant from the Tokiwa Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Acute myeloid leukemia is a hematological malignancy characterized by acquired genomic aberrations. Mutations in the <jats:italic>FMS-like tyrosine kinase 3<\/jats:italic> gene cause constitutive activation of downstream signaling pathways, thereby driving disease progression and conferring a poor prognosis. Gilteritinib, a tyrosine kinase inhibitor, is a promising treatment for <jats:italic>FMS-like tyrosine kinase 3<\/jats:italic>-mutated acute myeloid leukemia. However, gilteritinib resistance remains a significant concern, and its underlying mechanisms are not yet understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Case presentation<\/jats:title>\n            <jats:p>A 65-year-old Japanese male patient who was receiving regular hemodialysis developed pancytopenia in 2017. He required recurrent red blood cell transfusions due to anemia\u00a0in 2018. In 2019, he was diagnosed with myelodysplastic syndrome with excess blasts. We administered three courses of azacitidine but ceased it due to severe cytopenia. His disease had transformed to acute myeloid leukemia. The fourth course of azacitidine was administered, but it was ineffective. Since a tyrosine kinase domain mutation in <jats:italic>FMS-like tyrosine kinase 3<\/jats:italic> was detected in the acute myeloid leukemia cells, we administered gilteritinib at a dose of 120 mg. Although the treatment initially showed efficacy, the disease progressed, and he died 7 days after the initiation of gilteritinib. To assess the epigenetic changes in acute myeloid leukemia during the treatment with gilteritinb, we performed the assay for transposase-accessible chromatin with sequencing using the leukemia cells obtained from the patient before and after gilteritinib treatment. After the treatment, greater than fivefold changed assay for transposase-accessible chromatin peaks were detected in 137 (upregulated) and 105 (downregulated) regions. Among them, half of the regions were located in the intergenic regions. A Gene Ontology analysis of affected genes listed the mitogen\u2011activated protein kinase pathway, which is potentiated by the <jats:italic>FMS-like tyrosine kinase 3<\/jats:italic> genetic mutations in leukemia cells. No significant changes were noted at the <jats:italic>FMS-like tyrosine kinase 3<\/jats:italic> locus. On the gene locus of <jats:italic>PPP2R2B,<\/jats:italic> a known cancer-associated gene, the peaks were decreased, suggesting reduced chromatin accessibility. Conversely, upregulation peaks were observed on the gene locus and adjacent noncoding region of <jats:italic>PDGFD<\/jats:italic> that is associated with the progression of various types of cancer including acute myeloid leukemia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study demonstrated the epigenetic changes in acute myeloid leukemia cells that may be associated with gilteritinib resistance.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13256-025-05186-2","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T16:55:15Z","timestamp":1743699315000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessment of chromatin remodeling of acute myeloid leukemia cells treated with gilteritinib: a case report"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-5616","authenticated-orcid":false,"given":"Jinichi","family":"Mori","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koki","family":"Nojiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kanemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiro","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"5186_CR1","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","volume":"374","author":"E Papaemmanuil","year":"2016","unstructured":"Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et\u00a0al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209\u201321.","journal-title":"N Engl J Med"},{"key":"5186_CR2","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.bbmt.2017.04.020","volume":"23","author":"J Mori","year":"2017","unstructured":"Mori J, Yanada M, Uchida N, Fukuda T, Sakura T, Hidaka M, et\u00a0al. Outcomes of allogeneic hematopoietic cell transplantation in acute myeloid leukemia patients with abnormalities of the short arm of chromosome 17. Biol Blood Marrow Transplant. 2017;23:1398\u2013404.","journal-title":"Biol Blood Marrow Transplant"},{"key":"5186_CR3","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/nrc1169","volume":"3","author":"DL Stirewalt","year":"2003","unstructured":"Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. 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JHTF-2019-003.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors have no competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"153"}}