Cancer and Leukemia Group B - Leukemia Correlative Sciences

描述(由申请人提供)：CALGB白血病相关科学委员会(LCSC)的目标是将相关实验室研究成功地整合到CALGB白血病临床试验的设计和实施中。在本报告所述期间(2008年6月1日至2008年5月31日)，该委员会成员发现和/或验证了多种可用于风险适应患者临床试验和/或被视为治疗靶点的预后分子和细胞遗传学标记。委员会在本报告所述期间取得的科学进展得到162份出版物的支持(70份手稿和92份已出版或正在出版的摘要)。为了继续这项工作，在这项竞争性的续签申请中，CALGB LCSC请求支持三个已建立的核心(核心A：细胞遗传学；核心B：白血病组织库；核心C：管理)和四个项目，每个项目都使用来自参加CALGB白血病治疗方案的患者的材料。这一建议的一个共同主题是将已建立的预后标记与新发现的标记相结合，包括全基因组基因复制改变和基因和microRNA表达谱，以将急性髓系白血病(AML)、急性淋巴细胞白血病(ALL)和慢性淋巴细胞白血病(CLL)分解为可预测治疗反应和临床结果的分子亚群。此外，越来越多的数据表明，某些亚群的AML细胞具有类似于正常干细胞的高增殖能力和自我更新能力，因此可能介导抗白血病化疗的耐药。该委员会将首次采用一种相对新颖的策略来测试这些所谓的白血病干细胞(LSCs)的丰度和基因图谱与AML患者的治疗反应和临床结果的相关性。因此，在细胞遗传学核心和白血病组织库的支持下，这四个项目中的每一个都将解决将细胞遗传学和分子研究结果与白血病患者的诊断、治疗反应和生存相关的科学问题。这些项目由白血病生物学、诊断和治疗领域的杰出领导者领导：项目1：“成人AML的分子特征”(Pi Bloomfield/Marcucci)，项目2：“AML中白血病干细胞的功能和基因组特征”(Pi Armstrong)项目3：“成人ALL的全基因组分析”(Pi Downing)项目4：“早期状态和症状性CLL的分子、生化和免疫学研究”(Pi Byrd)。

DESCRIPTION (Provided by applicant): The goal of the CALGB Leukemia Correlative Sciences Committee (LCSC) is to attain a highly successful integration of correlative laboratory studies into the design and implementation of CALGB leukemia clinical trials. During the current reporting period (6/1/02-5/31/08), members of this Committee discovered and/or validated multiple prognostic molecular and cytogenetic markers that can be used for risk-adapted patients' stratification into clinical trials and/or be regarded as therapeutic targets. The scientific progress made by the LCSC during the current reporting period is supported by 162 publications (70 manuscripts and 92 abstracts published or in press). To continue this work, in this competing renewal application, the CALGB LCSC is requesting support for three established Cores (Core A: Cytogenetics; Core B: Leukemia Tissue Banking; Core C: Administration) and four projects, each of which utilizes material from patients that are enrolled on CALGB leukemia treatment protocols. A common theme of this proposal is the integration of the established prognostic markers with newly discovered markers, including genome-wide gene copy alterations and gene and microRNA expression profiles, to dissect acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL) into molecular subsets for which response to treatment and clinical outcome can be predicted. Furthermore, accumulating data indicate that certain subpopulations of AML cells have high proliferative potential and self-renewal capacity similar to normal stem cells and therefore could mediate resistance to anti-leukemia chemotherapy. This Committee will pursue for the first time a relatively novel strategy to test the relevance of abundance and gene profiles of these so-called leukemia stem cells (LSCs) to treatment response and clinical outcome of AML patients. Thus, with the support of the Cytogenetics core and the Leukemia Tissue Bank, each of the four projects will address scientific questions that correlate cytogenetic and molecular findings with leukemia patients' diagnosis, response to treatment and survival. The projects, led by outstanding leaders in the field of leukemia biology, diagnosis, and treatment are: Project 1: "Molecular characterization of adult AML" (PI Bloomfield/Marcucci,) Project 2: "Functional and genomic characterization of leukemia stem cells in AML" (PI Armstrong) Project 3: "Genome-wide analysis of adult ALL" (PI Downing) Project 4:"Molecular, biochemical, and immunologic studies of early state and symptomatic CLL" (PI Byrd).