Cellular and Molecular Studies of Leukemic Stem Cellss

白血病干细胞的细胞和分子研究

• 批准号: 6999328
• 负责人: Craig T. Jordan
• 金额: $ 27.38万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-16 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999328
• 关键词: Adenoviridae; NOD mouse; SCID mouse; acute myelogenous leukemia; antisense nucleic acid; apoptosis; gel mobility shift assay; human tissue; neoplasm /cancer genetics; neoplastic growth; nuclear factor kappa beta; salicylate; stem cells; transfection /expression vector; tumor suppressor proteins; western blottings

DESCRIPTION (provided by applicant): The past several years have seen a tremendous expansion in the field of stem cell biology. Numerous advances have occurred in understanding the biological relevance of stem cells, as well as their specific molecular properties. An important part of this new era in stem cell science relates directly to hematologic malignancies. Recent studies have led to the identification of a leukemic stem cell (LSC) population in patients with acute myelogenous leukemia (AML). LSCs are sufficient to perpetuate human leukemic cell growth in long-term culture assays and in the murine NOD/SCID model system. As a consequence of these data, it has been proposed that LSCs are central to the pathogenesis of human myeloid leukemia in vivo. Therefore, the primary objective of this application is to define novel molecular properties of LSCs and to exploit such properties to induce LSC-specific apoptosis. With this goal in mind, our studies have focused on defining unique characteristics of the LSC population. To date, we have shown that primitive AML cells aberrantly regulate several factors related to control of cell death decisions. Further, we have developed a model system in which primary AML cells are induced to undergo apoptosis, but normal cells are spared. Thus, we hypothesize that by targeting specific molecular events it will be possible to preferentially induce apoptosis in the LSC population. This hypothesis will be examined through experiments designed to: 1) characterize the molecular basis of apoptosis in primary AML cells, 2) expand strategies for preferential induction of LSC apoptosis, and 3) use molecular genetic strategies to define critical apoptosis control genes that function in LSCs. Collectively, these efforts will advance our understanding of basic mechanisms that underlie leukemic transformation and will improve strategies for the preferential ablation of LSCs.

描述（由申请人提供）：过去几年已经看到 干细胞生物学领域的巨大扩张。许多进步已有 发生在理解干细胞的生物学相关性以及 它们的特定分子特性。 STEM这个新时代的重要组成部分 细胞科学直接与血液学恶性肿瘤有关。最近的研究 导致患者的白血病干细胞（LSC）识别 伴有急性髓性白血病（AML）。 LSC足以使人类永存 长期培养测定法和鼠点头/scID中的白血病细胞生长 模型系统。由于这些数据，已经提出了LSC 在体内人类髓样白血病的发病机理至关重要。所以， 该应用的主要目的是定义新颖的分子 LSC的特性并利用此类特性诱导LSC特异性 凋亡。考虑到这个目标，我们的研究重点是定义独特 LSC人群的特征。迄今为止，我们已经证明了原始 AML细胞异常调节与控制细胞死亡有关的几个因素 决定。此外，我们开发了一个模型系统，其中原始AML细胞 被诱导会发生凋亡，但普通细胞幸免。因此，我们 假设通过靶向特定的分子事件，可以 优先诱导LSC种群凋亡。这个假设将是 通过设计为以下实验进行检查：1）表征分子基础 原代AML细胞中凋亡的凋亡，2）扩大优先的策略 LSC凋亡的诱导，3）使用分子遗传策略来定义 关键凋亡控制在LSC中起作用的基因。总的来说，这些 努力将促进我们对基本基本机制的理解 白血病转变，将改善优先的策略 LSC的消融。

项目成果

A new type of stochastic dependence revealed in gene expression data.

基因表达数据揭示了一种新型的随机依赖性。

• DOI: 10.2202/1544-6115.1189
• 发表时间: 2006
• 期刊: Statistical applications in genetics and molecular biology
• 影响因子: 0.9
• 作者: Klebanov,Lev;Jordan,Craig;Yakovlev,Andrei
• 通讯作者: Yakovlev,Andrei

Considerations for targeting malignant stem cells in leukemia.

• DOI: 10.1177/107327480401100216
• 发表时间: 2004-03
• 期刊: Cancer control : journal of the Moffitt Cancer Center
• 作者: M. Guzman;C. Jordan

Can we finally target the leukemic stem cells?

我们最终能靶向白血病干细胞吗？

• DOI: 10.1016/j.beha.2008.07.006
• 发表时间: 2008
• 期刊: Best practice & research. Clinical haematology
• 作者: Jordan,CraigT

Cancer stem cells.

癌症干细胞。

• DOI: 10.1097/01.jto.0000361758.17413.7c
• 发表时间: 2009
• 期刊: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
• 作者: Rudin,Charles;Minna,John
• 通讯作者: Minna,John