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CYTOKINE SIGNALING IN MYELOID LEUKEMIAS

粒细胞白血病中的细胞因子信号转导

基本信息

批准号：
2091961
负责人：
MICHAEL B LILLY
金额：
$ 10.51万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-08-01 至 1998-08-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2091961
关键词：
antisense nucleic acid apoptosis biological signal transduction colony stimulating factor cytokine gene expression hematopoietic growth factor myelogenous leukemia neoplasm /cancer immunology phenotype plasmids polymerase chain reaction recombinant proteins tissue /cell culture transfection western blottings

项目摘要

DESCRIPTION: (Adapted from applicant's abstract)This application seeks to characterize critical steps in the proliferative signalling pathways activated by GM-CSF in related cytokines in primitive myeloid cells. At least some cases of myeloid leukemia likely result from over activity of such signal pathways. Identification of critical or unique steps in such cascades may allow development of pharmacologic interventions to specifically disrupt these pathways. The specific hypothesis of this application is that expression of the pim-1 gene project, a 33 kd serine/threonine kinase, is necessary for effective proliferative signalling through GM-CSF and related receptors. The applicant further hypothesizes that pim-1 expression serves as a specific indicator of activation of such pathways. The hypothesis will be investigated by constructing cell systems which allow for the over expression or blockade of pim-1 activity. Factor-dependent myeloid cell lines will be transfected with plasmid constructs or retroviral constructs to allow autonomous expression of the pim-1 gene product.These lines will then be examined for factor- independent growth, impaired differentiation, inhibition of apoptosis and homotypic aggregation. Similar cell lines will be created utilizing plasmids containing antisense pim-1 constructs to inhibit activity of the endogenous pim-1 gene. These cells will be studied for the responsiveness to GM-CSF and related cytokines and their propensity to differentiation.

描述：(改编自申请人的摘要)本申请旨在描述增殖信号通路中的关键步骤在原始髓系细胞中被GM-CSF激活的相关细胞因子。在… 至少部分髓系白血病可能是由于过度活动所致这样的信号通路。确定以下方面的关键步骤或唯一步骤这样的级联可能允许开发药物干预措施来特别是破坏了这些通路。这一点的具体假设应用是Pim-1基因工程的表达，全长33kd 丝氨酸/苏氨酸激酶是有效增殖所必需的通过粒-巨噬细胞集落刺激因子及相关受体传递信号。申请人还进一步假设Pim-1的表达作为一种特定的指标激活这些通路。这一假设将由构建允许过度表达或阻断的细胞系统 Pim-1的活性。依赖因子的髓系细胞株将是用质粒构建体或逆转录病毒构建体转染以允许 Pim-1基因产物的自主表达。这些株系将接受不依赖因素的生长、分化障碍、抑制细胞凋亡和同型聚集。相似的细胞系将利用含有反义Pim-1结构的质粒来产生抑制内源性Pim-1基因的活性。这些细胞将是人粒-巨噬细胞集落刺激因子及其相关细胞因子的反应性研究有分化的倾向。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sodium vanadate, a tyrosine phosphatase inhibitor, affects expression of hematopoietic growth factors and extracellular matrix RNAs in SV40-transformed human marrow stromal cells.

钒酸钠是一种酪氨酸磷酸酶抑制剂，可影响 SV40 转化的人骨髓基质细胞中造血生长因子和细胞外基质 RNA 的表达。

DOI：
发表时间：
1992
期刊：
Experimental hematology
影响因子：
2.6
作者：
Andrews3rd,DF;Lilly,MB;Tompkins,CK;Singer,JW
通讯作者：
Singer,JW

Interleukin-6 and granulocyte-macrophage colony-stimulating factor are candidate growth factors for chronic myelomonocytic leukemia cells.

白介素6和粒细胞巨噬细胞集落刺激因子是慢性粒单核细胞白血病细胞的候选生长因子。

DOI：
发表时间：
1989
期刊：
Blood
影响因子：
20.3
作者：
Everson,MP;Brown,CB;Lilly,MB
通讯作者：
Lilly,MB

Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes.

粒细胞-巨噬细胞集落刺激因子和白细胞介素 3 对人中性粒细胞和单核细胞产生白细胞介素 8 的影响。

DOI：
发表时间：
1993
期刊：
Blood
影响因子：
20.3
作者：
Takahashi,GW;Andrews3rd,DF;Lilly,MB;Singer,JW;Alderson,MR
通讯作者：
Alderson,MR

Diphtheria toxin fused to granulocyte-macrophage colony-stimulating factor is toxic to blasts from patients with juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia.

与粒细胞巨噬细胞集落刺激因子融合的白喉毒素对幼年型粒单核细胞白血病和慢性粒单核细胞白血病患者的原始细胞具有毒性。

DOI：
发表时间：
1998
期刊：
Blood
影响因子：
20.3
作者：
Frankel,AE;Lilly,M;Kreitman,R;Hogge,D;Beran,M;Freedman,MH;Emanuel,PD;McLain,C;Hall,P;Tagge,E;Berger,M;Eaves,C
通讯作者：
Eaves,C

AN ANTIBODY THAT INHIBITS IN VITRO BONE MARROW PROLIFERATION IN A PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND APLASTIC ANEMIA

一种抑制系统性红斑狼疮和再生障碍性贫血患者体外骨髓增殖的抗体