BCL11 GENES IN NORMAL AND MALIGNANT B CELL DEVELOPMENT
正常和恶性 B 细胞发育中的 BCL11 基因
基本信息
- 批准号:6364329
- 负责人:
- 金额:$ 23.63万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-05-01 至 2006-04-30
- 项目状态:已结题
- 来源:
- 关键词:B lymphocyte Hodgkin's disease artificial chromosomes chronic lymphocytic leukemia developmental genetics embryogenesis fluorescent in situ hybridization gene induction /repression gene targeting genetically modified animals immunogenetics laboratory mouse leukopoiesis microarray technology monoclonal antibody natural gene amplification neoplasm /cancer genetics nonHodgkin's lymphoma protein isoforms protein protein interaction southern blotting transcription factor
项目摘要
DESCRIPTION (provided by applicant): Molecular cloning of chromosomal
translocations targeted to the immunoglobulin (IG) loci allows the
identification of genes of importance in the genesis of normal and malignant
B-cells. We have cloned a highly conserved zinc finger gene locus BCL11A, from
a chromosomal translocation, t(2;14)(p13;q32.3), that occurs as the sole
cytogenetic abnormality in rare and clinically aggressive subset of CLL. All
breakpoints involved IG gamma switch regions and clustered 5' of a CpG island
associated with BCL11A. BCL11A maps closely telomeric to REL and also appears
to be a target gene for amplifications and gains of 2p13 observed frequently in
Hodgkin's disease and in extranodal B-NHL. Together the data implicate
deregulated expression of BCL1 1A in the pathogenesis of divergent subtypes of
aggressive human cancers. There are three common BCL11A isoforms; each is a
transcriptional repressor and varies in the number of zinc fingers. BCL11A
interacts physically with and shares several similarities with BCL6, a gene
frequently translocated to both IG and non-IG associated sites. BCL1 1A shares
high identity with a human family member, BCL11B, on chromosome 14q32.1 and
with homologues across metazoan evolution. We propose to study the clinical
significance of deregulation BCL11 expression in malignancies with
abnormalities of chromosome 2p13 and to determine the function of BCL11 in
normal and malignant B-cell development Specific approaches include screening
for additional (BCL1 1A) and initial (BCL11B) cases containing
breaks/amplifications a these loci; functional analysis of transcriptional
mechanisms an downstream targets; assessing transforming activities using in
vitro and transgenic models; and inactivating the gene by targeted
disruption.
描述(申请人提供):染色体的分子克隆
针对免疫球蛋白(IG)基因座的易位允许
正常和恶性肿瘤发生过程中重要基因的鉴定
B细胞。我们克隆了一个高度保守的锌指基因基因座BCL11A,来自
一种染色体易位,t(2;14)(p13;q32.3),作为唯一的
罕见和临床侵袭性CLL亚群的细胞遗传学异常。全
断点涉及CpG岛的IG伽马切换区和聚集的5‘
与BCL11A相关。BCL11A将端粒紧密地映射到REL,也出现了
可作为2p13基因扩增和扩增的靶基因。
霍奇金病和结外B-NHL。这些数据加在一起就意味着
Bcl11a基因失调性表达在不同亚型白血病发病机制中的作用
侵袭性人类癌症。有三种常见的BCL11A亚型;每一种都是
转录抑制因子,锌指的数量也不同。BCL11A
与BCL6基因在身体上相互作用并有几个相似之处
经常被转移到IG和非IG关联站点。BCL1 1A股
与染色体14q32.1上的人类家族成员BCL11B高度同源性
与后生动物进化的同源物。我们建议进行临床研究。
Bcl11基因失调性表达在恶性肿瘤中的意义
染色体2p13异常与bcl11基因功能的关系
正常和恶性B细胞发育的特殊方法包括筛查
额外(BCL11A)和初步(BCL11B)个案包括
这些基因座的断裂/扩增;转录的功能分析
机制和下游目标;使用中评估转型活动
体外和转基因模型;以及通过靶向失活该基因
颠覆。
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)
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HALEY O TUCKER其他文献
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- 资助金额:
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- 资助金额:
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