Antiapoptotic function of WT1 in leukemia and development of WT1-targeting molecular targeted therapy

WT1在白血病中的抗凋亡作用及WT1分子靶向治疗的进展

• 批准号: 21591205
• 负责人: OJI
• 金额: $ 2.91万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591205/
• 关键词: WT1; leukemogenesis; molecular targeted therapy; apoptosis; antiapoptosis

The WT1 gene is overexpressed in leukemia and involved in leukemogenesis through its antiapoptotic functions. In the present study, proteomic analysis revealed that a protein which regulates metabolism of cancer cells was dephosphorylated in a leukemia cells with forced expression of WT1 17AA(+) isoform. Moreover, 60aa-long WT1-derived peptide induced apoptosis in leukemia cells. West-western analysis showed that this WT1-derived peptide bound directly to multiple proteins regulating metabolism of cancer cells. Moreover, forced expression of WT1 17AA(+) isoform increased these proteins. These results indicated that WT1 17AA(+) isoform was involved in cancer cell metabolism and the molecular mechanism of these functions of WT1 could be a target of novel molecular targeted therapy for leukemia.

WT 1基因在白血病中过表达，并通过其抗凋亡功能参与白血病发生。在本研究中，蛋白质组学分析显示，调节癌细胞代谢的蛋白质在具有WT 1 17 AA（+）同种型的强制表达的白血病细胞中被去磷酸化。此外，60 aa长的WT 1衍生肽诱导白血病细胞凋亡。West-western分析表明，这种WT 1衍生肽直接结合多种调节癌细胞代谢的蛋白质。此外，WT 117 AA（+）同种型的强制表达增加了这些蛋白质。这些结果表明WT 1 17 AA（+）亚型参与了肿瘤细胞的代谢，WT 1这些功能的分子机制可能成为白血病分子靶向治疗的新靶点。

项目成果

CD138-negative clonogenic cells are plasma cells but not B cells in some multiple myeloma patients

• DOI: 10.1038/leu.2012.80
• 发表时间: 2012-09-01
• 期刊: LEUKEMIA
• 影响因子: 11.4
• 作者: Hosen, N.;Matsuoka, Y.;Sugiyama, H.
• 通讯作者: Sugiyama, H.

Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes.

• DOI: 10.1016/j.leukres.2009.11.029
• 发表时间: 2009-11
• 期刊: Leukemia research
• 影响因子: 2.7
• 作者: H. Tamura;K. Dan;N. Yokose;R. Iwakiri;M. Ohta;H. Sakamaki;K. Tohyama;A. Kondo;Hideya Hyodo;Kyoko Nakamura;T. Yamashita;O. Elisseeva;Y. Oka;Y. Oji;H. Sugiyama;K. Ogata

Standardization of WT1 Immunohistochemical Staining and Evaluation of WT1 Positivity in Solid Cancers

实体瘤中 WT1 免疫组织化学染色的标准化和 WT1 阳性的评估

• 发表时间: 2011
• 作者: Oji Y;Berneman Z. N;Keilholz U;O' reilly R;Saglio G;Wagner N;Heike Y;Lundin E;Aozasa K;Pauwels P;Anguille S;Cilloni D;Ohashi H;Waelput W;Fukuda M;Tatsumi N;Oka Y;Sugiyama H.
• 通讯作者: Sugiyama H.

WT1 IgG antibody for early detection of nonsmall cell lung cancer and as its prognostic factor

• DOI: 10.1002/ijc.24367
• 发表时间: 2009-07-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Oji, Yusuke;Kitamura, Yayoi;Sugiyama, Haruo
• 通讯作者: Sugiyama, Haruo

WT1 Peptide Therapy for a Patient with Chemotherapy-resistant Salivary Gland Cancer

WT1 肽治疗化疗耐药唾液腺癌患者

• 发表时间: 2012
• 期刊: Anticancer Res
• 影响因子: 2
• 作者: Shirakata T;Oka Y;Nishida S;et al
• 通讯作者: et al