PROGRESSION OF CHRONIC MYELOGENOUS LEUKEMIA

描述（申请人描述）： 职业发展奖将 提供机会获得深入的培训和经验， 癌症和血液学研究的要点。拟议的培训包括 教学研究，专业会议，并与领导人合作， 癌症和白血病的研究领域。研究计划的目标是 提供学习癌症研究基本技术的机会， 恶性血液病，学会创造性地思考和分析， 并发展必要的技能，以发展一个成功的独立 研究计划。 Robert A.温伯格作为主要申办者，乔治博士 Q.戴利作为共同赞助商将提供出色的指导。温伯格医生 培训优秀调查员的既定记录。戴利医生有一个 在人类白血病的研究和作为临床 血液学家，他提供了一个很好的榜样，一个医生，科学家。的 怀特黑德研究所的教育机会和资源 生物医学研究提供的是优秀的，并将补充强者 温伯格博士和戴利博士的指导。 拟议的研究旨在解释慢性胰腺炎的临床过程， 骨髓性 白血病（CML）。 CML最初表现为临床上 可管理的慢性期疾病，其特征是过度增殖的 相对正常的细胞。CML不可避免地进展到急变期， 不可治愈的急性白血病 基因的变化导致了 进展到爆炸是未知的。 温伯格实验室最近开发了一种合作模式 人类细胞中的癌基因，表明原代人类细胞可以被 通过病毒癌基因、ras癌基因和 t e l o merase基因。 这个实验系统产生了一个人的模型， 致癌作用，可用于制定一些具体的，可测试的 可能解释慢性期CML进展为急变的假说 相位 根据对人类慢性期和急变期的观察， 细胞在免疫功能低下的NOD/SCID小鼠中以不同的方式移植， 关于慢性期CML的进展，可以在体内测试。 研究的前两部分阐述了端粒酶在肿瘤细胞中的作用。 CML的自然史后两部分探讨了癌基因在 探讨急变期CML的发病机制，并试图建立一个多步骤的模型， 解释慢性期CML向急变期的进展。

DESCRIPTION (Applicant's Description): A career development award will provide the opportunity to obtain in depth training and experience in the essentials of cancer and hematology research. The proposed training involves didactic study, professional meetings, and collaborations with leaders in the fields of cancer and leukemia research. The goal of the research plan is to provide an opportunity to learn basic techniques in the study of cancer and malignant hematologic diseases, to learn to think creatively and analytically, and to develop the skills necessary to develop a successful independent research program. The combination of Dr. Robert A. Weinberg as a primary sponsor and Dr. George Q. Daley as a co-sponsor will provide outstanding mentorship. Dr. Weinberg has an established record of training outstanding investigators. Dr. Daley has a strong background in the study of human leukemias and as a clinical hematologist he provides an excellent role model of a physician-scientist. The educational opportunities and the resources that the Whitehead Institute for Biomedical Research provides are outstanding, and will complement the strong mentorship of Dr. Weinberg and Dr. Daley. The proposed research seeks to explain the clinical course of chronic myelogenous leukemia (CML). CML initially manifests as a clinically manageable chronic phase disease, characterized by a hyperproliferation of relatively normal cells. CML inevitably progresses to blast phase, a virtually u n t reatable acute leukemia. The genetic changes responsible for the progression to blast are unknown. The Weinberg laboratory has recently developed a model for cooperating oncogenes in human cells, demonstrating that primary human cells can be transformed by the combination of a viral oncogene, a ras oncogene, and the t e l o merase gene. This experimental system yields a model of human carcinogenesis that can be used to formulate a number of specific, testable hypotheses that may explain the progression of chronic phase CML to blast phase. Building on the observation that human chronic phase and blast phase cells engraft differently in the immunocompromised NOD/SCID mouse, hypotheses regarding the progression of chronic phase CML can be tested in vivo. The first two parts of the research address the role of telomerase in the natural history of CML. The second two parts explore the role of oncogenes in the pathogenesis of blast phase CML and attempt to build a multi-step model to explain the progression of chronic phase CML to blast phase.