Role of the Wilms' tumor gene WT1 in human leukemogenesis

维尔姆斯氏肿瘤基因 WT1 在人类白血病发生中的作用

• 批准号: 13470205
• 负责人: SUGIYAMA Haruo
• 金额: $ 9.02万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470205/
• 关键词: WT1; leukemia; tumor marker; 32D; oncogene; leukemogenesis; single-cell RT-PCR; ウィルムス腫瘍遺伝子; CD34; G2; M; cell cycle

1. The wild-type WT1 gene is expressed in almost all leukemias and thus WT1mRNA is a pan-leukemia tumor marker.2. The growth of leukemia cells was inhabited by the treatment with WT1 antisense oligomers.3. Constitutive expression of the wild-type WT1 gene inhibited differentiation of 32D c13 myeloid progenitor cells and instead induced proliferation of the cells in response to G-CSF.4. Normal myeloid progenitor cells transfected with the wild-type WT1 cDNA-integrated retroviral vetcor formed more CFU-G, CFU-M, and CFU-GM colonies compared to those transfected with control vector in response to G-CSF.5. To determine the frequencies of WT1-expressing bone marrow cells, 1,632 CD34^+ human bone marrow progenitor cells were examined for the WT1 expression by using single-cell RT-PCR. Only 19 (1.2%) of the 1,632 CD34^+ cells expressed WT1mRMA and the WT1mRMA expression levels were similar between normal CD34^+ and leukemia single cells, suggesting that WT1-expressing CD34^+ cells were normal counterparts of WT1-expressing leukemia cells.

1.野生型WT 1基因在几乎所有的白血病中都有表达，因此WT 1 mRNA是一种泛白血病肿瘤标志物. WT 1反义寡聚体处理白血病细胞后，白血病细胞的生长受到抑制.野生型WT 1基因的组成型表达抑制32 D c13髓系祖细胞的分化，并诱导细胞响应G-CSF的增殖。野生型WT 1 cDNA整合的逆转录病毒载体转染的正常髓系祖细胞在G-CSF刺激下形成的CFU-G、CFU-M和CFU-GM集落数均高于对照组。为了确定表达WT 1的骨髓细胞的频率，使用单细胞RT-PCR检测了1，632个CD 34 ^+人骨髓祖细胞的WT 1表达。在1，632个CD 34 ^+细胞中，只有19个（1.2%）表达WT 1 mRMA，正常CD 34 ^+和白血病单细胞的WT 1 mRMA表达水平相似，这表明表达WT 1的CD 34 ^+细胞是表达WT 1的白血病细胞的正常对应物。

项目成果

Li, H., et al.: "The Ick promoter-driven expression of the Wilms' tumor gene WT1 blocks intrathymic differentiation of T-lineage cells"International Journal of Hematology. (in press).

Li, H., 等人：“Wilms 肿瘤基因 WT1 的 Ick 启动子驱动的表达阻断了 T 谱系细胞的胸腺内分化”《国际血液学杂志》。

Sugiyama, H.: "The wilms' tumor gene : its oncogenic function and clinical application"International Journal of Hematology. 73. 177-187 (2001)

Sugiyama, H.：“维尔姆斯肿瘤基因：其致癌功能和临床应用”国际血液学杂志。

Hosen, N., et al.: "Very low frequencies of human normal CD34+ hematopoietic progenitor cells express the Wilms' tumor gene WT1 at the levels comaprable to those in leukemia cells"British Journal of Hematology.. 116. 409-420 (2002)

Hosen, N. 等人：“极低频率的人类正常 CD34 造血祖细胞以与白血病细胞相当的水平表达肾母细胞瘤基因 WT1”《英国血液学杂志》.. 116. 409-420 (2002

Hosen, N.: "Very low frequencies of human normal CD34^+ hematopoietic progenitor cells express the Wilms' tumor gene WT1 at the levels comaprable to those in leukemia cells"British Journal of Hematology. 116. 409-420 (2002)

Hosen，N.：“人类正常CD34+造血祖细胞以与白血病细胞相当的水平表达维尔姆斯肿瘤基因WT1的频率非常低”《英国血液学杂志》。

Ueda, T.: "Overexpression of the Wilms' tumor gene WT1 in human bone and soft-tissue sarcomas"Cancer Science. (in press).

Ueda, T.：“维尔姆斯肿瘤基因 WT1 在人骨和软组织肉瘤中的过度表达”癌症科学。