Molecular mechanisms of multi-step leukemogenesis in Down syndrome

唐氏综合症多步白血病发生的分子机制

• 批准号: 17013004
• 负责人: ITO Etsuro
• 金额: $ 30.08万
• 依托单位: Hirosaki 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-17013004/
• 关键词: ダウン症候群; 白血病; 転写因子; GATA1; 21番染色体; TMD; WL-DS; BACH1; STAT3; KIT; JAK3; 急性巨核球性白血病; AML1; RUNX1; AMKL

To understand the mechanism of leukemogensis in Down syndrome, we investigate the genes on chromosome 21 and identified ERG, RUNX1 and BACH1 as the candidates of the causative genes. JAK3 activating mutations were identified in about 10% of preleukemia (TMD) in Down syndrome. GATA1 mutations affected the expression levels of GATA1s protein. GATA1s low mutations in TMD were significantly associated with a risk of progression to acute megakaryoblastic leukemia and lower WBC counts.

为了了解唐氏综合症白血病发生的机制，我们研究了21号染色体上的基因，并确定ERG、RUNX 1和BACH 1为致病基因的候选基因。JAK3激活突变在唐氏综合征的白血病前期（TMD）中约有10%。GATA1突变影响GATA1s蛋白的表达水平。TMD中GATA 1低突变与进展为急性巨核细胞白血病和低WBC计数的风险显著相关。

项目成果

Cloning and Characterization of the Novel Chimeric Gene p53/FXR2 in the Acute Megakaryoblastic Leukemia Cell Line CMK11-5.

急性巨核细胞白血病细胞系 CMK11-5 中新型嵌合基因 p53/FXR2 的克隆和表征。

• 发表时间: 2006
• 期刊: Tohoku J Exp Med. 209巻
• 作者: Kanezaki R;Toki T;Xu G;Narayanan R;Ito E.
• 通讯作者: Ito E.

Platelet-derived growth factor may be associated with fibrosis in a Down syndrome patient with transient myeloproliferative disorder.

血小板衍生生长因子可能与患有短暂性骨髓增殖性疾病的唐氏综合症患者的纤维化有关。

• 发表时间: 2008
• 期刊: Eur J Haematol 81巻
• 作者: Ogawa J;Kanegane H;Tsuneyama K;Kanezaki R;Futatani T;Nomura K;Ishizawa S;Sasahara M;Ito E;Miyawaki T.
• 通讯作者: Miyawaki T.

Molecular and clinical characterization of cardio-facio-cutaneous (CFC) syndrome:: Overlapping clinical manifestations with Costello syndrome

• DOI: 10.1002/ajmg.a.31658
• 发表时间: 2007-04-15
• 期刊: AMERICAN JOURNAL OF MEDICAL GENETICS PART A
• 影响因子: 2
• 作者: Narumi, Yoko;Aoki, Yoko;Matsubara, Yokhi
• 通讯作者: Matsubara, Yokhi

Voriconazole for both successful treatment of disseminated Trichosporon asahii infection and subsequent cord blood transplantation in an infant with acute myelogenous leukemia

• DOI: 10.1038/bmt.2010.96
• 发表时间: 2011-02
• 期刊: Bone Marrow Transplantation
• 影响因子: 4.8
• 作者: K. Kudo;K. Terui;S. Sasaki;T. Kamio;T. Sato;E. Ito

Array-based genomic resequencing of human leukemia

• DOI: 10.1038/onc.2010.117
• 发表时间: 2010-06-24
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Yamashita, Y.;Yuan, J.;Mano, H.
• 通讯作者: Mano, H.