Elucidation of molecular pathogenesis and therapeutic targets for refractory hematological malignancies

阐明难治性血液恶性肿瘤的分子发病机制和治疗靶点

• 批准号: 19679004
• 负责人: KUROKAWA Mineo
• 金额: $ 64.31万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (S)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19679004/
• 关键词: 白血病; 造血幹細胞; 白血病幹細胞; 血液腫瘍学; Evi-1; Runx1; NF-κB; 血液種瘍学; AML1

In this study, we demonstrated that the epigenetic regulation of transcription by Evi-1 is essential for its leukemogenic capacity. We also revealed the novel molecular mechanisms by which the loss-of-function of AML1 promotes leukemogenesis, using our Aml1 conditional knockout mice. Furthermore, using newly generated Evi-1 conditional knockout mice and Evi-1-ires-GFP knock-in mice, we demonstrated a distinctive relationship between Evi-1 and the phenotype of hematopoietic stem cells or leukemic stem cells. These results provide a foundation to develop novel molecular targeted therapies for refractory hematological malignancies.

在这项研究中，我们证明了 Evi-1 转录的表观遗传调控对其致白血病能力至关重要。我们还利用 Aml1 条件性敲除小鼠揭示了 AML1 功能丧失促进白血病发生的新分子机制。此外，使用新产生的Evi-1条件敲除小鼠和Evi-1-ires-GFP敲入小鼠，我们证明了Evi-1与造血干细胞或白血病干细胞表型之间的独特关系。这些结果为开发针对难治性血液恶性肿瘤的新型分子靶向疗法奠定了基础。

项目成果

Pretransplant Predictors and Posttransplant Sequels of Acute Kidney Injury after Allogeneic Stem Cell Transplantation

• DOI: 10.1016/j.bbmt.2010.07.010
• 发表时间: 2011-03-01
• 期刊: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
• 影响因子: 4.3
• 作者: Kagoya, Yuki;Kataoka, Keisuke;Kurokawa, Mineo
• 通讯作者: Kurokawa, Mineo

Beneficial and Adverse Effects of Molecularly Targeted Therapies for Acute Promyelocytic Leukemia in Central Nervous System

• DOI: 10.2174/187152709789541943
• 发表时间: 2009-11-01
• 期刊: CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
• 影响因子: 3
• 作者: Nagai, Sumimasa;Takahashi, Tsuyoshi;Kurokawa, Mineo
• 通讯作者: Kurokawa, Mineo

Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic haematopoietic SCT

• DOI: 10.1038/bmt.2010.48
• 发表时间: 2010-12-01
• 期刊: BONE MARROW TRANSPLANTATION
• 影响因子: 4.8
• 作者: Ueda, K.;Watadani, T.;Kurokawa, M.
• 通讯作者: Kurokawa, M.

The impact of molecularly targeted therapies upon the understanding of leukemogenesis and the role of hematopoietic stem cell transplantation in acute promyelocytic leukemia.

分子靶向治疗对理解白血病发生的影响以及造血干细胞移植在急性早幼粒细胞白血病中的作用。

• 发表时间: 2010
• 期刊: Current Stem Cell Research & Therapy
• 影响因子: 2.7
• 作者: Nagai S;Takahashi T;Kurokawa M.
• 通讯作者: Kurokawa M.

Nilotinib-induced hypothyroidism in a patient with chronic myeloid leukemia

慢性粒细胞白血病患者尼洛替尼诱发的甲状腺功能减退症

• DOI: 10.1007/s12185-011-0790-2
• 发表时间: 2011
• 期刊: International Journal of Hematology
• 影响因子: 2.1
• 作者: Yoshizato T;Nannya Y;Yoshiki Y;Nakamura F;Imai Y;Ichikawa M;Kurokawa M
• 通讯作者: Kurokawa M