| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2025-12-03 |
| タイトル |
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タイトル |
H3K27me3 and HOXA9 expression predict prognosis in pediatric acute myeloid leukemia: an epigenetic-transcriptional correlation study |
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言語 |
en |
| 言語 |
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言語 |
eng |
| キーワード |
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言語 |
en |
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キーワード |
AML |
| キーワード |
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言語 |
en |
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キーワード |
H3K27me3 |
| キーワード |
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言語 |
en |
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キーワード |
H3K4Me3 |
| キーワード |
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言語 |
en |
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キーワード |
HOXA cluster genes |
| キーワード |
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言語 |
en |
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キーワード |
HOXA9 |
| キーワード |
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言語 |
en |
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キーワード |
pediatric |
| 資源タイプ |
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資源タイプ |
journal article |
| アクセス権 |
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アクセス権 |
open access |
| 著者 |
Goto, Hironori
Suenobu, Souichi
Koga, Yuhki
| en |
Koga, Yuhki（Personal）
National Hospital Organization Nishibeppu National Hospital
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Search repository
Yamamoto, Shunsuke
Nakashima, Kentaro
Oba, Utako
Hasegawa, Daiichiro
Usami, Ikuya
| en |
Usami, Ikuya（Personal）
Hyogo Prefectural Amagasaki General Medical Center
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Search repository
Yamamori, Ayako
盛武, 浩
WEKO
28692
e-Rad_Researcher
40336300
| ja |
盛武, 浩
宮崎大学
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| ja-Kana |
モリタケ, ヒロシ
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| en |
Moritake, Hiroshi
University of Miyazaki
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Search repository
Nobusawa, Sumihito
Okuno, Keisuke
Kawaguchi, Koji
Kanno, Miyako
Ishida, Hisashi
Cho, Yuko
Nishida, Haruto
Tomizawa, Daisuke
| en |
Tomizawa, Daisuke（Personal）
National Center for Child Health and Development
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Search repository
Ihara, Kenji
Ohga, Shouichi
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Background: Epigenetic dysregulation plays a central role in pediatric acute myeloid leukemia (AML), yet its clinical relevance remains underexplored. This study primarily aimed to elucidate the clinical effect of H3K27me3 and H3K4me3 status on pediatric acute myeloid leukemia. We evaluated the prognostic impact of H3K27me3 and H3K4me3 histone trimethylation, along with associated gene expression profiles, in pediatric AML.
Methods: We retrospectively analyzed 74 children with newly diagnosed non-FAB M3 and non-Down syndrome AML in a prolonged cohort in Japan. Bone marrow immunohistochemistry assessed H3K27me3 and H3K4me3 expression levels. RNA sequencing was successfully performed on sorted leukemic blasts in six representative cases, owing to limited sample availability. Chemoresistance and epigenetic modulation were evaluated in AML cell lines treated with GSK-J4, a histone demethylase inhibitor.
Results: High H3K27me3 expression at diagnosis was significantly associated with superior overall and event-free survival over three years (OS HR 8.0; EFS HR 5.0; both p < 0.01). H3K4me3 levels at diagnosis showed no prognostic impact. Among 14 KMT2A-rearranged cases, all six patients with high H3K27me3 achieved a long-term first remission (median follow-up: 10 years), whereas those with low expression had higher relapse rates. Transcriptomic analysis revealed upregulation of HOXA9, and HOXA-cluster genes and downregulation of ABCB1, in low H3K27me3 samples. In vitro, GSK-J4 increased H3K27me3 and suppressed HOXA9 expression in KG-1 cells, enhancing sensitivity to cytarabine.
Conclusion: Low H3K27me3 expression defines a poor-risk group in pediatric AML, potentially via HOXA9-driven dysregulation. H3K27me3 may serve as a prognostic biomarker and potential therapeutic target. |
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言語 |
en |
| 書誌情報 |
en : Frontiers in Hematology
巻 4,
p. 1668408,
発行日 2025-09-25
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| 出版者 |
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出版者 |
Frontiers Media SA |
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言語 |
en |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
28133935 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.3389/frhem.2025.1668408 |
| 著者版フラグ |
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出版タイプ |
VoR |
Fulltext (7.4 MB)
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