G-CSFR MUTATIONS--A NOVEL MECHANISM OF LEUKEMOGENESIS
G-CSFR MUTATIONS--A NOVEL MECHANISM OF LEUKEMOGENESIS
批准号:
2382809
负责人:
Belinda Rene Avalos
金额:
$14.6万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-08-01 至 1999-07-31
关键词:
acute myelogenous leukemia carcinogenesis clinical research colony stimulating factor enzyme activity gene mutation growth factor receptors guanine nucleotide binding protein human genetic material tag human subject mitogen activated protein kinase neoplasm /cancer genetics phosphatidylinositol 3 kinase polymerase chain reaction
中文摘要
描述:(改编自研究者的摘要)遗传病变
英文摘要
DESCRIPTION: (adapted from the investigator's abstract) Genetic lesions
involving an increasing number of oncogenes have been recognized to play a
role in the development of human leukemias. These lesions result in
disruption of the normal function of genes or in their inappropriate
expression. Most of the oncogenes which have been studied in acute
myelogenous leukemia (AML) encode proteins that function either as
intracellular signaling molecules or as transcription factors, and play a
role in the regulation of cell proliferation, differentiation, and survival.
Mutations of the granulocyte colony-stimulating factor receptor (G-CSFR)
gene have recently been reported in patients with AML and provide the first
link between abnormal cytokine receptors and clinical AML. These mutations
which result in truncations of the carboxy-terminal region of the G-CSFR
disrupt the maturation signaling function of the normal wild-type G-CSFR and
lead to hyperproliferative responses to G-CSF through a dominant-negative
mechanism. Such lesions represent a novel mechanism of leukemogenesis.
The frequency of mutations in the G-CSFR gene in patients with AML is at
present unknown. Likewise, little is known about the mechanisms that
promote the dominant-negative phenotype or the signaling pathways that
mediate enhanced growth responses to G-CSF by mutant G-CSFR forms from
patients with AML. Experiments are proposed here to better understand the
signaling events associated with growth regulation by the G-CSFR and the
mechanisms by which mutations in the G-CSFR gene result in unregulated cell
proliferation. Studies will also be done to determine the frequency of
G-CSFR mutations in patients with AML. This information will clarify the
role of G-CSFR mutations in the pathogenesis of AML, permit the formulation
of rational guidelines for appropriate clinical use of G-CSF in patients
with AML, and may reveal potential novel therapeutic targets for the
treatment of AML.
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G-CSF Receptor and Ubiquitination
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批准号:6984691
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项目类别:
-
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
-
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:
-
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
-
依托单位:
LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
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批准号:6514159
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项目类别:
-
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 G-CSFR IN AML
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批准号:6377439
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项目类别:
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资助金额:$20.82万
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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:2748953
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项目类别:
-
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:
-
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:
-
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:
-
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
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批准号:3087365
-
项目类别:
-
资助金额:$6.48万
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财政年份:1986
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负责人:Belinda Rene Avalos
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依托单位:
海外基金