Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome

田中, 龍彦

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Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome

http://hdl.handle.net/10129/0002000721

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Item type

リポジトリ登録用アイテムタイプ（シンプル）(1)

公開日

2024-12-25

タイトル

Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome

言語

eng

キーワード

言語

主題Scheme

Other

主題

Myeloid leukemia

キーワード

言語

主題Scheme

Other

主題

Oown syndrome

キーワード

言語

主題Scheme

Other

主題

azacitidine

キーワード

言語

主題Scheme

Other

主題

chemotherapy

資源タイプ

資源タイプ識別子

http://purl.org/coar/resource_type/c_db06

資源タイプ

doctoral thesis

アクセス権

open access

アクセス権URI

http://purl.org/coar/access_right/c_abf2

著者

田中, 龍彦

抄録

内容記述タイプ

Abstract

内容記述

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.

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内容記述

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内容記述

Author: Tatsuhiko Tanaka, Ko Kudo, Rika Kanezaki, Kentaro Yuzawa, Tsutomu Toki, Ryo Okuse, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Kiminori Terui, Etsuro Ito

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内容記述

内容記述タイプ

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内容記述

Citation: Experimental Hematology :132 :104179, Apr 2024

言語

書誌情報

en : Experimental Hematology

巻 132, p. 104179, 発行日 2024-02-09

ISSN

収録物識別子タイプ

EISSN

収録物識別子

1873-2399

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Ver.1

2025-01-06 08:10:10.755972

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Antileukemic effect of azacitidine, a DNA methyltransferase inhibitor, on cell lines of myeloid leukemia associated with Down syndrome

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