Genetic Dissection of Tumor Progression in NF-1 AML
Genetic Dissection of Tumor Progression in NF-1 AML
批准号:
6469488
负责人:
CAMILYNN I BRANNAN
金额:
$25.81万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-05-01 至 2006-04-30
关键词:
acute myelogenous leukemia computer simulation gene mutation gene targeting genetic mapping genetically modified animals laboratory mouse molecular cloning molecular site neoplasm /cancer genetics neoplastic process neurofibromatosis type 1 protein /gene oncoproteins pediatric neoplasm /cancer polymerase chain reaction protein structure function protooncogene pulsed field gel electrophoresis
中文摘要
描述:(申请人提供)青少年粒单核细胞白血病(JMML)是
一种发生在幼儿中的疾病,与高死亡率有关
费率。在大多数患者中,JMML有一个渐进的病程,通过
感染、出血或进展为急性髓系白血病(AML)的优点。
众所周知,患有1型神经纤维瘤病(NF1)的儿童有一种
患JMML的风险显著增加,我们能够开发出一种小鼠
用造血干细胞重建致死性照射小鼠的JMML模型
NFL基因功能缺失突变的纯合子细胞。在课程中
在这些实验中,我们发现所有这些基因上相同的
重组的小鼠出现了一种类似JMML的疾病,但只有一小部分继续
发展出更多的急性疾病。这一结果有力地表明,
基因损伤是疾病进展的原因。这件事的重点是
建议确定这些额外的遗传损伤作为一种更好的手段
了解白血病的进展情况。为了实现这一目标,我们将NF1
BXH-2小鼠遗传背景上的突变,一种已知含有
具有躯体感染性的嗜生态逆转录病毒。利用这种强大的体细胞
突变系统,我们鉴定了三种常见的生态型前病毒
整合(EPI)站点。我们假设这些EPI站点将允许
鉴定与髓系肿瘤进展有关的基因。我们有
四个具体目标:具体目标1:确定病毒在EPIL中的整合
位点导致c-myb基因的失控。
特定目标2:确定被病毒整合中断的基因
Epi2基因座。
具体目标3:确定被病毒整合中断的基因
Ep3基因座。
具体目标4:确定更多与肿瘤进展有关的EPI位点
JMML。
英文摘要
DESCRIPTION: (provided by applicant) Juvenile myelomonocytic leukemia (JMML) is
a disease that occurs in young children and is associated with a high mortality
rate. In most patients, JMML has a progressive course leading to death by
virtue of infection, bleeding or progression to acute myeloid leukemia (AML).
As it is known that children with Neurofibromatosis type 1 (NF1) have a
markedly increased risk of developing JMML, we were able to develop a mouse
model of JMML by reconstituting lethally irradiated mice with hematopoetic stem
cells homozygous for a loss of function mutation in the Nfl gene. In the course
of these experiments, we found that all these genetically identical
reconstituted mice developed a JMML-like disorder, but only a subset went on to
develop more acute disease. This result strongly suggests that additional
genetic lesions are responsible for disease progression. The focus of this
proposal is to identify these additional genetic lesions as a means to better
understand leukemic progression. Toward this goal, we have placed the Nf1
mutation on the BXH-2 mouse genetic background, a strain known to contain a
somatically infectious ecotropic retrovirus. Using this powerful somatic
mutagenesis system, we have identified three common ecotropic proviral
integration (Epi) sites. We hypothesize that these Epi sites will allow
identification of genes that are involved in myeloid tumor progression. We have
four specific aims: Specific Aim 1:Determine if viral integration at the Epil
site leads to deregulation of the c-myb gene.
Specific Aim 2:Characterize the gene interrupted by viral integrations at the
Epi2 locus.
Specific Aim 3: Characterize the gene interrupted by viral integrations at the
Epi3 locus.
Specific Aim 4: Identify additional Epi sites involved in tumor progression of
JMML.
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会议论文
GENETIC COMPLEMENTATION OF A MOUSE MODEL FOR PWS
-
批准号:6388130
-
项目类别:
-
资助金额:$27.6万
-
财政年份:1999
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
GENETIC COMPLEMENTATION OF A MOUSE MODEL FOR PWS
-
批准号:2884429
-
项目类别:
-
资助金额:$26.05万
-
财政年份:1999
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
GENETIC COMPLEMENTATION OF A MOUSE MODEL FOR PWS
-
批准号:6181892
-
项目类别:
-
资助金额:$26.82万
-
财政年份:1999
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
MOUSE MODELS OF HUMAN PWS/AS IMPRINTING CENTER MUTATIONS
-
批准号:2634827
-
项目类别:
-
资助金额:$18.15万
-
财政年份:1997
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
MOUSE MODELS OF HUMAN PWS/AS IMPRINTING CENTER MUTATIONS
-
批准号:2023844
-
项目类别:
-
资助金额:$17.94万
-
财政年份:1997
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
MOUSE MODELS OF HUMAN PWS/AS IMPRINTING CENTER MUTATIONS
-
批准号:6342930
-
项目类别:
-
资助金额:$19.79万
-
财政年份:1997
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
MOUSE MODELS OF HUMAN PWS/AS IMPRINTING CENTER MUTATIONS
-
批准号:2857268
-
项目类别:
-
资助金额:$18.68万
-
财政年份:1997
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
MOUSE MODELS OF HUMAN PWS/AS IMPRINTING CENTER MUTATIONS
-
批准号:6138544
-
项目类别:
-
资助金额:$19.23万
-
财政年份:1997
-
负责人:CAMILYNN I BRANNAN
-
依托单位:
海外基金