Inactivating EVI1 for the Treatment of Myelodysplastic *

灭活 EVI1 用于治疗骨髓增生异常 *

基本信息

  • 批准号:
    7487814
  • 负责人:
  • 金额:
    $ 36.74万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2005
  • 资助国家:
    美国
  • 起止时间:
    2005-09-30 至 2010-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by Applicant): Myelodysplastic syndrome (MDS) is a group of stem cell malignancies most frequent among elderly patients and has a high annual incidence among hematological malignancies with approximately 14,000 new cases diagnosed every year. About 30%-40% of MDS progresses to acute myeloid leukemia (AML). However, the majority of patients succumb from infection or bleeding or treatment complications within 3-5 years. With the increase of life expectancy due to improving medical care, there has been a significant increase in the frequency of MDS and at this time the incidence of MDS (about 5 per 100,000) is higher than that of chronic myelogenous leukemia (CML) or AML in the same age group. The genetic events that drive this disease are not known, however a translocation of chromosome band 3 q26 is a recurring abnormality seen in about 10% of MDS. This genomic site contains EVI1, a gene inappropriately activated in MDS by the chromosomal rearrangement. EVI1-positive MDS patients develop fatal hematopoietic defects rapidly evolving to AML and in general their survival is less than one year. In terms of the biological mechanisms which characterize MDS, it is generally thought that the MDS cell has impaired differentiation and increased apoptosis. As the disease evolves, the cells have increased deregulated proliferation and decreased apoptosis, remain immature, and the number of blast cells increases. The lack of an animal model that reproduces MDS has strongly limited our understanding of this disease. Recent work by our group has generated a significant animal model of MDS by forcing the expression of EVI1 in murine bone marrow (BM) cells. The mice show features of MDS including hypercellular BM, BM apoptosis, and severe cytopenia and anemia. In contrast to what observed in patients, the EVI1-ppsitive murine MDS does not evolve to AML and therefore provides a unique system to understand the disease at a stage which is still potentially treatable. Preliminary studies with this model have given clear clues about molecular pathways that affect erythropoiesis, platelet formation, and cell cycling immediately after expression of EVI1 and suggest that in the EVI1-positive mice the disease progresses from a viable early stage in which the erythropoietic lineage is compromised, to an always fatal late stage characterized by anemia, apoptosis, severe cytopenia, BM apoptosis, leading to death. The specific aims are designed to identify key steps in this progression that could be used to block the advancement of MDS and to follow the response to treatment of MDS patients. They include the identification of the molecular pathways that disrupt hematopoiesis in EVI1-positive BM cells (first aim) and of the genes that are activated or repressed by EVI1 (second aim). The third aim will be focused on the role of arsenic trioxide in the treatment of EVI1-positive MDS and on the isolation of small molecules that inhibit EVI1.
描述(由申请人提供):

项目成果

期刊论文数量(0)
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Giuseppina Nucifora其他文献

Giuseppina Nucifora的其他文献

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{{ truncateString('Giuseppina Nucifora', 18)}}的其他基金

A Mouse Model of Myelodysplastic Syndrome Progression
骨髓增生异常综合征进展的小鼠模型
  • 批准号:
    7465550
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
Inactivating EVI1 for the Treatment of Myelodysplastic *
灭活 EVI1 用于治疗骨髓增生异常 *
  • 批准号:
    7278665
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
A Mouse Model of Myelodysplastic Syndrome Progression
骨髓增生异常综合征进展的小鼠模型
  • 批准号:
    7650235
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
Inactivating EVI1 for the Treatment of Myelodysplastic *
灭活 EVI1 用于治疗骨髓增生异常 *
  • 批准号:
    7128100
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
Inactivating EVI1 for the Treatment of Myelodysplastic *
灭活 EVI1 用于治疗骨髓增生异常*
  • 批准号:
    7022781
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
A Mouse Model of Myelodysplastic Syndrome Progression
骨髓增生异常综合征进展的小鼠模型
  • 批准号:
    7082227
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
A Mouse Model of Myelodysplastic Syndrome Progression
骨髓增生异常综合征进展的小鼠模型
  • 批准号:
    6984724
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
A Mouse Model of Myelodysplastic Syndrome Progression
骨髓增生异常综合征进展的小鼠模型
  • 批准号:
    7261916
  • 财政年份:
    2005
  • 资助金额:
    $ 36.74万
  • 项目类别:
EVI1 Expression is a Prognostic Marker of CML
EVI1 表达是 CML 的预后标志物
  • 批准号:
    6750118
  • 财政年份:
    2003
  • 资助金额:
    $ 36.74万
  • 项目类别:
EVI1 Expression is a Prognostic Marker of CML
EVI1 表达是 CML 的预后标志物
  • 批准号:
    6610092
  • 财政年份:
    2003
  • 资助金额:
    $ 36.74万
  • 项目类别:

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    3556971
  • 财政年份:
    1980
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