EVI1 Expression is a Prognostic Marker of CML

EVI1 表达是 CML 的预后标志物

基本信息

  • 批准号:
    6610092
  • 负责人:
  • 金额:
    $ 15.59万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-07-01 至 2005-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Chronic myelogenous leukemia (CML) is a disease characterized by an initial chronic phase during which there is an abnormal proliferation of myeloid cell lineage. This treatable phase in general lasts 2-5 years, but without treatment it will inexorably progress to a final blast (or accelerated) phase for which there is no known treatment. The inappropriate expression of the EVI1 gene appears in the majority of CML patients. For a long time, the treatment of choice for CML was IFN-alpha, however recently a new drug, STI571, targets and inhibits the BCP/ABL activity in the leukemic cells. Because of increasing frequency of STI571 resistance, current NIH-sponsored clinical trials study a combination of STI571 and IFN-alpha in treatment of CML. The EVI1 gene is not detected in normal hematopoietic bone marrow but is expressed in about 30% to 80% of CML patients. We showed that EVI1 is an aggressive oncogene. New advances in our work indicate that EVI1 abrogates the effects of IFN-alpha in vitro, that IFN-alpha-resistant chronic phase CML patients express EVI1, and that the forced expression of EVI1 in IFN-alpha hematopoietic cell lines abrogates the growth-inhibitory response to IFN-alpha. Taken together, these data provide the first clear correlation between a CML-associated gene and the failure to respond to IFN-alpha inhibition. Based on the background presented, we propose that CML patients who inappropriately express EVI1 will not respond to IFN-alpha therapy alone or in combination with STI571. It is also possible that the EVI1-positive patients treated with STI571 and IFN-alpha could actually be harmed because treatment with IFN-alone will preclude the use of the alternative drug Cytarabine also used in clinical trials in combination with STI571. The goal of this proposal is to design a sensitive routine test to identify CML patients who express EVI1 and who therefore will not benefit from IFN-alpha therapy. The goals are: First, we will define the best experimental conditions for quantification of the expression of EVI1 in leukemia and control samples. Second, we will determine whether EVI1 expression in chronic phase patients induces a faster progression of the disease to the blast phase. Real-time RT-PCR analysis and statistical analysis of CML and control samples will be used for this study.
描述(申请人提供):慢性粒细胞白血病(CML)是一种疾病,其特征是在最初的慢性期有髓系细胞系的异常增殖。这种可治疗阶段一般持续2-5年,但如果不进行治疗,它将不可避免地进展到最后的冲击期(或加速阶段),目前还没有已知的治疗方法。EVI1基因的异常表达存在于大多数CML患者中。长期以来,CML的首选治疗方法是干扰素-α,然而最近一种新药STI571靶向并抑制了白血病细胞中的BCP/ABL活性。由于STI571耐药频率的增加,目前由美国国立卫生研究院赞助的临床试验研究STI571和干扰素-α的联合治疗慢性粒细胞白血病。EVI1基因在正常骨髓中未检测到,但在约30%至80%的CML患者中表达。我们发现EVI1是一种侵袭性癌基因。我们工作的新进展表明,EVI1在体外取消了干扰素-α的作用,干扰素-α耐药的慢性期CML患者表达EVI1,并且EVI1在干扰素-α造血细胞系中的强制表达取消了对干扰素-α的生长抑制反应。综上所述,这些数据首次明确提供了慢性粒细胞白血病相关基因与干扰素-α抑制反应失败之间的关联。基于本文提出的背景,我们认为不适当表达EVI1的CML患者不会单独接受干扰素-α治疗或与STI571联合治疗。接受STI571和干扰素-α治疗的EVI1阳性患者实际上也可能受到伤害,因为单独使用干扰素治疗将排除将替代药物阿糖胞苷与STI571联合使用的可能性。这项提议的目标是设计一种敏感的常规测试来识别表达EVI1的CML患者,这些患者因此不会从干扰素-α治疗中受益。我们的目标是:首先,我们将确定EVI1在白血病和对照样本中表达的最佳实验条件。其次,我们将确定EVI1在慢性期患者中的表达是否会导致疾病更快地进展到急变期。本研究将采用实时定量RT-PCR方法对慢性粒细胞白血病和对照样本进行分析和统计分析。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Giuseppina Nucifora其他文献

Giuseppina Nucifora的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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:
    $ 15.59万
  • 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:
    7487814
  • 财政年份:
    2005
  • 资助金额:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 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:
    $ 15.59万
  • 项目类别:

相似海外基金

FAIRClinical: FAIR-ification of Supplementary Data to Support Clinical Research
FAIRClinical:补充数据的 FAIR 化以支持临床研究
  • 批准号:
    EP/Y036395/1
  • 财政年份:
    2024
  • 资助金额:
    $ 15.59万
  • 项目类别:
    Research Grant
The IDeA State Consortium for a Clinical Research Resource Center: Increasing Clinical Trials in IDeA States through Communication of Opportunities, Effective Marketing, and WorkforceDevelopment
IDeA 州临床研究资源中心联盟:通过机会交流、有效营销和劳动力发展增加 IDeA 州的临床试验
  • 批准号:
    10715568
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Optimizing integration of veterinary clinical research findings with human health systems to improve strategies for early detection and intervention
优化兽医临床研究结果与人类健康系统的整合,以改进早期检测和干预策略
  • 批准号:
    10764456
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
The Mayo Clinic NeuroNEXT Clinical Research Site
梅奥诊所 NeuroNEXT 临床研究网站
  • 批准号:
    10743328
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Addressing Underperformance in Clinical Trial Enrollments: Development of a Clinical Trial Toolkit and Expansion of the Clinical Research Footprint
解决临床试验注册表现不佳的问题:开发临床试验工具包并扩大临床研究足迹
  • 批准号:
    10638813
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
The Minnesota TMD IMPACT Collaborative: Integrating Basic/Clinical Research Efforts and Training to Improve Clinical Care
明尼苏达州 TMD IMPACT 协作:整合基础/临床研究工作和培训以改善临床护理
  • 批准号:
    10828665
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Improving Multicultural Engagement in Clinical Research through Partnership with Federally Qualified Health Centers and Community Health Worker Programs
通过与联邦合格的健康中心和社区卫生工作者计划合作,改善临床研究中的多元文化参与
  • 批准号:
    10823828
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Promoting a Culture Of Innovation, Mentorship, Diversity and Opportunity in NCI Sponsored Clinical Research: NCI Research Specialist (Clinician Scientist) Award Application of Janice M. Mehnert, M.D.
在 NCI 资助的临床研究中促进创新、指导、多样性和机会文化:Janice M. Mehnert 医学博士的 NCI 研究专家(临床科学家)奖申请
  • 批准号:
    10721095
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Clinical Research Center for REstoration of NEural-based Function in the Real World (RENEW)
现实世界神经功能恢复临床研究中心 (RENEW)
  • 批准号:
    10795328
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
Clinical Research and Academic Success in Obstetrics & Gynecology
产科临床研究和学术成就
  • 批准号:
    10828252
  • 财政年份:
    2023
  • 资助金额:
    $ 15.59万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了