CYTOKINE SIGNALING IN MYELOID LEUKEMIAS

粒细胞白血病中的细胞因子信号转导

• 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
• 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

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）此申请寻求 在增殖信号通路中表征关键步骤 在原始髓样细胞中的相关细胞因子中被GM-CSF激活。在 至少有些髓样白血病可能是由于过度活动而引起的 这种信号途径。 确定关键或独特步骤 这种级联可能允许开发药理干预措施 特别破坏这些途径。 特定假设 应用是PIM-1基因项目的表达，一个33 kD 丝氨酸/苏氨酸激酶是有效增殖所必需的 通过GM-CSF和相关受体的信号传导。 申请人进一步 假设PIM-1表达是 这种途径的激活。 该假设将通过 构建允许过度表达或封锁的单元系统 PIM-1活性。 因子依赖性髓样细胞系将是 用质粒构建或逆转录病毒构建体转染 然后，PIM-1基因产物的自主表达。 检查因素独立生长，分化受损， 抑制细胞凋亡和同型聚集。 类似的细胞系 将使用含有反义PIM-1构建体的质粒创建 抑制内源性PIM-1基因的活性。 这些细胞将是 研究了对GM-CSF及其相关细胞因子及其的反应性 分化的倾向。

项目成果

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。

• 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。

• 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

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。

• 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

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。

• 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

Pentoxifylline inhibits tumor necrosis factor-alpha-mediated cytotoxicity and cytostasis in L929 murine fibrosarcoma cells.

Pentoxifylline 抑制 L929 鼠纤维肉瘤细胞中肿瘤坏死因子-α 介导的细胞毒性和细胞抑制。

• DOI: 10.1016/0192-0561(94)90092-2
• 发表时间: 1994
• 期刊: International journal of immunopharmacology
• 作者: Takahashi,GW;Montgomery,RB;Stahl,WL;Crittenden,CA;Valentine,MA;Thorning,DR;Andrews3rd,DF;Lilly,MB
• 通讯作者: Lilly,MB