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:(改编自研究者摘要)遗传性病变
涉及越来越多的癌基因已被确认发挥作用,
在人类白血病发展中的作用。 这些病变导致
基因正常功能的破坏或其不适当的
表情 大多数已经在急性胰腺炎中研究过的癌基因
骨髓性白血病(AML)编码的蛋白质,
细胞内信号分子或转录因子,并发挥作用,
在调节细胞增殖、分化和存活中的作用。
粒细胞集落刺激因子受体(G-CSFR)突变
最近报道了AML患者的基因,并提供了第一个
异常细胞因子受体与临床AML之间的联系。 这些突变
其导致G-CSFR的羧基末端区域的截短
破坏正常野生型G-CSFR的成熟信号功能,
导致对G-CSF过度增殖反应
机制 这种病变代表了白血病发生的一种新机制。
AML患者中G-CSFR基因突变的频率为
目前未知。 同样地,我们也不知道
促进显性阴性表型或信号通路,
介导增强的生长反应,以G-CSF的突变体G-CSFR形式从
AML患者。 这里提出实验以更好地理解
与G-CSFR的生长调节相关的信号传导事件和
G-CSFR基因突变导致不受调控的细胞增殖的机制
增殖 还将进行研究,以确定
AML患者中的G-CSFR突变。 这些信息将澄清
G-CSFR突变在AML发病机制中的作用,
G-CSF在患者中适当临床使用的合理指南
与AML,并可能揭示潜在的新的治疗靶点,
AML的治疗。
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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专著(0)
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会议论文
G-CSF Receptor and Ubiquitination
-
批准号:6984691
-
项目类别:
-
资助金额:$18.69万
-
财政年份:2005
-
负责人:Belinda Rene Avalos
-
依托单位:
G-CSF Receptor and Ubiquitination
-
批准号:7140531
-
项目类别:
-
资助金额:$18.25万
-
财政年份:2005
-
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
-
项目类别:
-
资助金额:$21.44万
-
财政年份:1999
-
负责人:Belinda Rene Avalos
-
依托单位:
LOSS OF NEGATIVE SIGNALING BY THE G-CSFR IN AML
-
批准号:6174121
-
项目类别:
-
资助金额:$20.21万
-
财政年份:1999
-
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:6377439
-
项目类别:
-
资助金额:$20.82万
-
财政年份:1999
-
负责人:Belinda Rene Avalos
-
依托单位:
LOSS OF NEGATIVE SIGNALING BY THE GCSFR IN AML
-
批准号:2899455
-
项目类别:
-
资助金额:$17.08万
-
财政年份:1999
-
负责人:Belinda Rene Avalos
-
依托单位:
G-CSFR MUTATIONS--A NOVEL MECHANISM OF LEUKEMOGENESIS
-
批准号:2748953
-
项目类别:
-
资助金额:$14.55万
-
财政年份:1997
-
负责人:Belinda Rene Avalos
-
依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
-
批准号:3087369
-
项目类别:
-
资助金额:$6.26万
-
财政年份:1987
-
负责人:Belinda Rene Avalos
-
依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
-
批准号:3087368
-
项目类别:
-
资助金额:$6.95万
-
财政年份:1987
-
负责人:Belinda Rene Avalos
-
依托单位:
HUMAN ERYTHROID-POTENTIATING ACTIVITY
-
批准号:3087366
-
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: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