{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T06:14:18Z","timestamp":1785651258353,"version":"3.56.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The molecular pathogenesis of acute myeloid leukemia (AML) was dramatically clarified over the latest two decades. Several important molecular markers were discovered in patients with AML that have helped to improve the risk stratification. However, developing new treatment strategies for relapsed\/refractory acute myeloid leukemia (AML) is crucial due to its poor prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>To overcome this difficulty, we performed an assay for transposase\u2010accessible chromatin with sequencing (ATAC\u2010seq) in 10 AML patients with various gene alterations. ATAC\u2010seq is based on direct in vitro sequencing adaptor transposition into native chromatin, and is a rapid and sensitive method for integrative epigenomic analysis. ATAC\u2010seq analysis revealed increased accessibility of the <jats:italic>DOCK1<\/jats:italic> gene in patients with AML harboring poor prognostic factors. Following the ATAC\u2010seq results, quantitative reverse transcription polymerase chain reaction was used to measure <jats:italic>DOCK1<\/jats:italic> gene expression levels in 369 pediatric patients with de novo AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High <jats:italic>DOCK1<\/jats:italic> expression was detected in 132 (37%) patients. The overall survival (OS) and event\u2010free survival (EFS) among patients with high <jats:italic>DOCK1<\/jats:italic> expression were significantly worse than those patients with low <jats:italic>DOCK1<\/jats:italic> expression (3\u2010year EFS: 34% vs. 60%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001 and 3\u2010year OS: 60% vs. 80%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). To investigate the significance of high <jats:italic>DOCK1<\/jats:italic> gene expression, we transduced <jats:italic>DOCK1<\/jats:italic> into MOLM14 cells, and revealed that cytarabine in combination with DOCK1 inhibitor reduced the viability of these leukemic cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results indicate that a DOCK1 inhibitor might reinforce the effects of cytarabine and other anti\u2010cancer agents in patients with AML with high <jats:italic>DOCK1<\/jats:italic> expression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31151","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T08:27:42Z","timestamp":1719908862000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High <i>DOCK1<\/i> expression identifies a distinct prognostic subgroup of pediatric acute myeloid leukemia: Results of the Japanese Pediatric Leukemia\/Lymphoma Study Group AML\u201005 trial"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6598-8694","authenticated-orcid":false,"given":"Masahiro","family":"Yoshitomi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yokohama City University Graduate School of Medicine  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010Ichi","family":"Tsujimoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yokohama City University Graduate School of Medicine  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junji","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yokohama City University Graduate School of Medicine  Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Kawai","sequence":"additional","affiliation":[{"name":"Department of Maternal\u2010Fetal Biology National 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