Research & Development of molecular target therapy for leukemia and Its assessment System

研究

• 批准号: 17016029
• 负责人: NAOE Tomoki
• 金额: $ 29.38万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17016029/
• 关键词: 白血病; シグナル伝達; 幹細胞; 分子標的治療; キメラ転写因子; FLT3; STAT; 急性前骨髄球性白血病; マウスモデル; 急性前骨髓球性白血病; PML-RARα; 転写抑制複合体; キメラ転写物; 転写抑制; 免疫不全マウス; 治療法

For the development of more effective and secure target therapy for leukemia, we clarified that mutated FLT3 and KIT, and N-CoR/HDAC3/TBLR1 complex that is recruited by chimera transcription factor PML-RARA are ideal target molecules/complex for therapy. We developed FLT3 inhibitors, FI-700 and KW-2449, and KIT inhibitor, KI-328. For targeting N-CoR/HDAC3/TBLR1 complex we designed a decoy peptide. We also established a laboratory system which can evaluate p-FLT3 or p-STAT5 of leukemia cells using FACS and estimate pharmaco-dynamismly plasma bioassay system.

为了开发更有效和安全的白血病靶向治疗方法，我们阐明了突变的FLT 3和KIT以及嵌合体转录因子PML-RARA募集的N-CoR/HDAC 3/TBLR 1复合物是理想的治疗靶分子/复合物。我们开发了FLT 3抑制剂FI-700和KW-2449，以及KIT抑制剂KI-328。针对N-CoR/HDAC 3/TBLR 1复合物，我们设计了一个诱饵肽。建立了流式细胞仪检测白血病细胞p-FLT 3或p-STAT 5的实验室系统和药效学评价的血浆生物测定系统。

项目成果

Retention but significant reduction of BCR-ABL transcript in hematopoietic stem cells in chronic myelogenous leukemia after imatinib therapy

• DOI: 10.1007/s12185-008-0221-1
• 发表时间: 2008-12-01
• 期刊: INTERNATIONAL JOURNAL OF HEMATOLOGY
• 影响因子: 2.1
• 作者: Abe, Akihiro;Minami, Yosuke;Naoe, Tomoki
• 通讯作者: Naoe, Tomoki

BMI-1 Is Highly Expressed in M0-Subtype Acute Myeloid Leukemia.

BMI-1 在 M0 亚型急性髓系白血病中高表达。

• 发表时间: 2005
• 期刊: Int.J.Hematol. 82
• 作者: Sawa;M.;Yamamoto;K.;Yokozawa;T.;Kiyoi;H.;Hishida;A.;Kajiguchi;T.;Seto;M.;Kohno;A.;Kitamura;K.;Itoh;Y.;Asou;N.;Hamajima;N.;Emi;N.;Naoe;T.
• 通讯作者: T.

Genomewide array-based comparative genomic hybridization analysis of acute promyelocytic leukemia

• DOI: 10.1002/gcc.20309
• 发表时间: 2006-04-01
• 期刊: GENES CHROMOSOMES & CANCER
• 影响因子: 3.7
• 作者: Karnan, S;Tsuzuki, S;Naoe, T
• 通讯作者: Naoe, T

FLT3/ITD Regulates Leukemia Cell Adhesion throughα4β1 Integrin and Pyk2 Signalin

FLT3/ITD 通过 α4β1 整合素和 Pyk2 信号蛋白调节白血病细胞粘附

• 发表时间: 2009
• 作者: Katsumi A;Naoe T;et al.
• 通讯作者: et al.

KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation

• DOI: 10.1182/blood-2009-01-199307
• 发表时间: 2009-08-20
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Shiotsu, Yukimasa;Kiyoi, Hitoshi;Naoe, Tomoki
• 通讯作者: Naoe, Tomoki