{"created":"2024-12-25T07:39:59.688150+00:00","id":2000721,"links":{},"metadata":{"_buckets":{"deposit":"96c8dc85-8349-452f-a36d-4259b7fd278e"},"_deposit":{"created_by":11,"id":"2000721","owner":"11","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"2000721"},"status":"published"},"_oai":{"id":"oai:hirosaki.repo.nii.ac.jp:02000721","sets":["557:666:1733727873643"]},"author_link":[],"control_number":"2000721","item_1735019115310":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Myeloid leukemia associated with Down syndrome (ML-DS) responds well to chemotherapy and has a favorable prognosis, but the clinical outcome of patients with refractory or relapsed ML-DS is dismal. We recently reported a case of relapsed ML-DS with an effective response to a  DNA methyltransferase inhibitor, azacitidine (AZA). However, the efficacy of AZA for refractory or relapsed ML-DS remains uncertain. Here, we investigated the effects and mechanism of action of AZA on three ML-DS cell lines derived from relapsed cases. AZA inhibited the proliferation of  all examined ML-DS cell lines to the same extent as that of AZA-sensitive acute myeloid leukemia non-Down syndrome cell lines. Transient low-dose AZA treatment exerted durable antileukemic effects on ML-DS cells. The inhibitory effect included cell cycle arrest, apoptosis, and reduction  of aldehyde dehydrogenase activity. Comprehensive differential gene expression analysis showed that AZA induced megakaryocytic differentiation in all ML-DS cell lines examined. Furthermore, AZA induced activation of type I interferon-stimulated genes, primarily involved in antiproliferation signaling, without stimulation of the interferon receptor-mediated autocrine system. Activation of the type I interferon pathway by stimulation with interferon-α exerted antiproliferative effects on ML-DS cells, suggesting that AZA exerts its antileukemic effects on ML-DS cells at least partially through the type I interferon pathway. Moreover, the effect of AZA on normal hematopoiesis did not differ significantly between individuals with non-Down syndrome and Down syndrome. In summary, this study suggests that AZA is a potentially effective treatment option for ML-DS disease control, including relapsed cases, and has reduced side effects.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_1735020952570":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"10.1016/j.exphem.2024.104179","subitem_relation_type_select":"DOI"}}]},"item_30001_access_rights4":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_30001_bibliographic_information17":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2024-02-09","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"104179","bibliographicVolumeNumber":"132","bibliographic_titles":[{"bibliographic_title":"Experimental Hematology","bibliographic_titleLang":"en"}]}]},"item_30001_creator2":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"田中, 龍彦","creatorNameLang":"ja"}]}]},"item_30001_date_granted20":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2024-09-30"}]},"item_30001_degree_grantor21":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"弘前大学"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"11101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_30001_degree_name19":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_30001_description8":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"Author: Tatsuhiko Tanaka, Ko Kudo, Rika Kanezaki, Kentaro Yuzawa, Tsutomu Toki, Ryo Okuse, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Kiminori Terui,  Etsuro Ito","subitem_description_language":"en","subitem_description_type":"Other"},{"subitem_description":"Citation: Experimental Hematology :132 :104179, Apr 2024","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_30001_dissertation_number18":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第2296号"}]},"item_30001_file22":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-25"}],"fileDate":[{"fileDateType":"Available","fileDateValue":"2025-04-30"}],"filename":"tdm_2296_tanaka.pdf","filesize":[{"value":"7.1 MB"}],"format":"application/pdf","licensetype":"license_5","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://hirosaki.repo.nii.ac.jp/record/2000721/files/tdm_2296_tanaka.pdf"},"version_id":"9ea5ce02-8d46-4578-b6f1-7f4105afb58b"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-25"}],"filename":"tdm_2296_tanaka_a1.pdf","filesize":[{"value":"180 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"内容要旨","objectType":"abstract","url":"https://hirosaki.repo.nii.ac.jp/record/2000721/files/tdm_2296_tanaka_a1.pdf"},"version_id":"93479aff-ee65-4cf1-be84-d7e5a4135042"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2024-12-25"}],"filename":"tdm_2296_tanaka_a2.pdf","filesize":[{"value":"298 KB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"審査要旨","objectType":"abstract","url":"https://hirosaki.repo.nii.ac.jp/record/2000721/files/tdm_2296_tanaka_a2.pdf"},"version_id":"171ee366-68b7-41c2-96a5-d17e66ac86db"}]},"item_30001_language10":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_30001_resource_type11":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_30001_rights5":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"© 2024 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.","subitem_rights_language":"en"}]},"item_30001_source_identifier16":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1873-2399","subitem_source_identifier_type":"EISSN"}]},"item_30001_subject7":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Myeloid leukemia","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Oown syndrome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"azacitidine","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"chemotherapy","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_30001_title0":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome","subitem_title_language":"en"}]},"item_30001_version_type12":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_title":"Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome","item_type_id":"40034","owner":"11","path":["1733727873643"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2024-12-25"},"publish_date":"2024-12-25","publish_status":"0","recid":"2000721","relation_version_is_last":true,"title":["Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2025-04-30T06:18:06.629440+00:00"}