LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
批准号:
6377439
负责人:
Belinda Rene Avalos
金额:
$20.82万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-09-23 至 2003-06-30
中文摘要
描述:(逐字改编自调查人员的摘要)
在理解生长抑制方面已经取得了相当大的进展
调节免疫反应的受体发出的信号,人们对此知之甚少
造血细胞因子介导“负性”信号的机制
感受器。最近,粒细胞集落刺激因子中的点突变
因子受体(G-CSFR)基因缺失的远端生长抑制域
在急性髓系白血病(AML)患者中检测到G-CSFR
这会导致对G-CSF的超敏反应,并促进细胞增殖。这些
SERVER先于AML的患者中已发现100%的突变
先天性中性粒细胞减少症(SCN)这些突变普遍存在于
SCN转化为AML的患者亚群提供了强有力的证据
它们有助于这一亚群患者的白血病转化。
来自G-CSFR的生长抑制信号的精确性质
在急性髓系白血病患者中,这些基因的表达被打乱仍不清楚。此外,这个角色
G-CSFR突变在无先证者急性髓系白血病发病中的作用
SCN还没有得到充分的研究。这里提出的实验是为了更好地
了解G-CSFR和G-CSFR调节负面信号的机制
G-CSFR突变在白血病发生中的作用。此信息将
为急性髓细胞白血病的病因机制提供进一步的见解,允许
制定更明确的指南,以便临床适当使用G-CSF
在急性髓系白血病患者中,并可能揭示治疗急性髓细胞白血病的新的治疗靶点
急性髓系白血病的治疗。
英文摘要
DESCRIPTION: (adapted verbatim from the investigator's abstract) Although
considerable advances have been made in understanding growth inhibitory
signaling by receptors that regulate immune responses, little is known about
the mechanisms that mediate "negative" signaling by hematopoietic cytokine
receptors. Recently, point mutations in the granulocyte colony-stimulating
factor receptor (G-CSFR) gene deleting the distal growth inhibitory domain of
the G-CSFR have been detected in patients with acute myelogenous leukemia (AML)
that result in hypersensitivity to G-CSF and enhanced cell proliferation. These
mutations have been identified in 100% of patients with AML preceded by server
congenital neutropenia (SCN). The universal occurrence of these mutations in
the subset of patients with SCN transforming to AML provides strong evidence
that they contribute to leukemic transformation in this subset of patients.
The precise nature of the growth inhibitory signals derived from the G-CSFR
which are disrupted in patients with AML remain unknown. Additionally, the role
of G-CSFR mutations in the development of AML in patients without antecedent
SCN has not been adequately studied. Experiments are proposed here to better
understand the mechanisms that regulate negative signaling by the G-CSFR and
the contribution of G-CSFR mutations to leukemogenesis. This information will
provide further insights into etiologic mechanisms underlying AML, permit the
formulation of better defined guidelines for appropriate clinical use of G-CSF
in patients with AML, and may reveal novel therapeutics targets for the
treatment of AML.
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会议论文
G-CSF Receptor and Ubiquitination
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批准号:6984691
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项目类别:
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资助金额:$18.69万
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财政年份:2005
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负责人:Belinda Rene Avalos
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依托单位:
G-CSF Receptor and Ubiquitination
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批准号:7140531
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项目类别:
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资助金额:$18.25万
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财政年份:2005
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负责人:Belinda Rene Avalos
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依托单位:
LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
-
批准号:6514159
-
项目类别:
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资助金额:$21.44万
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财政年份:1999
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负责人:Belinda Rene Avalos
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依托单位:
LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
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批准号:6174121
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项目类别:
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资助金额:$20.21万
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财政年份:1999
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负责人:Belinda Rene Avalos
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依托单位:
LOSS OF NEGATIVE SIGNALING BY THE GCSFR IN AML
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批准号:2899455
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项目类别:
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资助金额:$17.08万
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财政年份:1999
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负责人:Belinda Rene Avalos
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依托单位:
G-CSFR MUTATIONS--A NOVEL MECHANISM OF LEUKEMOGENESIS
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批准号:2382809
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项目类别:
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资助金额:$14.6万
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财政年份:1997
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负责人:Belinda Rene Avalos
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依托单位:
G-CSFR MUTATIONS--A NOVEL MECHANISM OF LEUKEMOGENESIS
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批准号:2748953
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项目类别:
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资助金额:$14.55万
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财政年份:1997
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负责人:Belinda Rene Avalos
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依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
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批准号:3087369
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项目类别:
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资助金额:$6.26万
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财政年份:1987
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负责人:Belinda Rene Avalos
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依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
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批准号:3087368
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项目类别:
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资助金额:$6.95万
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财政年份:1987
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负责人:Belinda Rene Avalos
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依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
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批准号:3087366
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项目类别:
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资助金额:$7.33万
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财政年份:1987
-
负责人:Belinda Rene Avalos
-
依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
-
批准号:3087367
-
项目类别:
-
资助金额:$7.33万
-
财政年份:1987
-
负责人:Belinda Rene Avalos
-
依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
-
批准号:3087365
-
项目类别:
-
资助金额:$6.48万
-
财政年份:1986
-
负责人:Belinda Rene Avalos
-
依托单位:
海外基金