Prognostic implications of the genetic abnormalities in adult patients with acute lymphoblastic leukemia

成人急性淋巴细胞白血病患者遗传异常的预后意义

• 批准号: 23591396
• 负责人: ASOU Norio
• 金额: $ 3.24万
• 依托单位: Saitama Medical University (2013)Kumamoto University (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591396/
• 关键词: 急性リンパ性白血病; IKZF1遺伝子; エピゲノム; EED遺伝子; CREBBP遺伝子; TP53遺伝子; フィラデルフィア染色体; 予後予測; ヒストン; H3K27; CREBBP; EED; TP53; BCR-ABL; ALL; CBP; IKZF1; PAX5; JAK2; PRC2; EZH2

The aim in this study is to establish a prognostic scoring system based on the genetic abnormalities in adult patients with acute lymphoblastic leukemia (ALL). Recently, comprehensive gene analysis in pediatric ALL brought new genetic abnormalities such as IKZF1 and CREBBP. In this study, alterations in the IKZF1 gene were frequently detected in adult ALL (53%) compared to that of pediatric ALL. Although no mutation in the epigenetic modifiers such as UTX, SUZ12, RPD3 or EZH2 was found, mutations in the EED and CREBBP were detected in adult ALL. 5-year relapse-free survival in patients without mutation, with one mutation and with two or more mutations in the IKZF1, EED, CREBBP or TP53 genes was 47%, 22% and 0%, respectively, indicating that these gene mutations confer a poor clinical outcome in adult Philadelphia chromosome-negative ALL.

本研究的目的是建立一个基于成人急性淋巴细胞白血病（ALL）患者遗传异常的预后评分系统。 最近，儿童 ALL 的综合基因分析带来了新的基因异常，例如 IKZF1 和 CREBBP。 在这项研究中，与儿童 ALL 相比，成人 ALL (53%) 中经常检测到 IKZF1 基因的改变。 尽管未发现UTX、SUZ12、RPD3或EZH2等表观遗传修饰因子发生突变，但在成人ALL中检测到了EED和CREBBP突变。 IKZF1、EED、CREBBP 或 TP53 基因无突变、有一种突变和两种或两种以上突变的患者的 5 年无复发生存率分别为 47%、22% 和 0%，表明这些基因突变导致成人费城染色体阴性 ALL 的临床结果较差。

项目成果

IKZF1 deletions in adult B-cell acute lymphoblastic leukemia.

成人 B 细胞急性淋巴细胞白血病中的 IKZF1 缺失。

• 发表时间: 2011
• 作者: Aoki Y,Ikeda H;Ishida T;et al;Tokunaga K.
• 通讯作者: Tokunaga K.

Clonal heterogeneity and evolution of acute myeloid leukemia during disease progression

急性髓系白血病疾病进展过程中的克隆异质性和进化

• 发表时间: 2013
• 作者: Kihara R;Hoshino H;Suzuki K;Chen F;Kato T;Miyawaki S;Asou N;Taki T;Taniwaki M;Naoe T;Kiyoi H
• 通讯作者: Kiyoi H

Prognostic impact of FLT3, CEBPA, NPM1, IDH1 and IDH2 gene mutations in patients with AML.

FLT3、CEBPA、NPM1、IDH1 和 IDH2 基因突变对 AML 患者的预后影响。

• 发表时间: 2012
• 作者: Yamaguchi S;Iwanaga E;Tokunaga K;Nanri T;Shimomura T;Suzushima H;Mitsuya H;Asou N.
• 通讯作者: Asou N.

Expression of CD56 is an unfavorable prognostic factor for acute promyelocytic leukemia with higher initial white blood cell counts.

• DOI: 10.1111/cas.12319
• 发表时间: 2014-01
• 期刊: Cancer science
• 影响因子: 5.7
• 作者: Ono T;Takeshita A;Kishimoto Y;Kiyoi H;Okada M;Yamauchi T;Emi N;Horikawa K;Matsuda M;Shinagawa K;Monma F;Ohtake S;Nakaseko C;Takahashi M;Kimura Y;Iwanaga M;Asou N;Naoe T;Japan Adult Leukemia Study Group
• 通讯作者: Japan Adult Leukemia Study Group

Crebbp HAT domain mutations are frequently detected in adult acute lymphoblastic leukemia

Crebbp HAT 结构域突变在成人急性淋巴细胞白血病中经常检测到

• 发表时间: 2012
• 作者: Tokunaga K;Yamaguchi S;Iwanaga E;Nanri T;Shimomura T;Suzushima H;Mitsuya H;and Asou N
• 通讯作者: and Asou N