MLL translocations in t-AML

t-AML 中的 MLL 易位

• 批准号: 6459980
• 负责人: NANCY J ZELEZNIK-LE
• 金额: $ 26.34万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-20 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6459980
• 关键词: acute myelogenous leukemia; bone marrow; cell differentiation; chimeric proteins; disease /disorder model; drug carcinogenesis; drug related neoplasm /cancer; fusion gene; hematopoietic stem cells; human subject; human tissue; laboratory mouse; molecular oncology; neoplastic transformation; oncogenes; phenotype; point mutation; site directed mutagenesis; tissue /cell culture

Therapy-related leukemias following treatment with drugs that target DNA toposiomerase II frequently involve translocations of the MLL gene on chromosome band 11q23. This research project will focus on functional analysis of MLL translocations, with a major focus on the MLL-CBP translocation. MLL-CBP was cloned as the MLL fusion present in patients with a t(11;16) (q23;p13). With one exception, these patients had therapy-related leukemia, and a substantial proportion presented with t-MDS. We recently developed murine model systems for the in vitro and in vivo analysis of the MLL-CBP fusion. This project involves studies to further delineate critical functions contributed by CBP to the fusion protein, to determine the functional effects of domain swapping on leukemia and pre-leukemia phenotype, and to determine the effects of the MLL-CBP fusion on hematopoietic cell lineage commitment and survival.

使用靶向 DNA 拓扑异构酶 II 的药物治疗后的治疗相关性白血病经常涉及染色体带 11q23 上 MLL 基因的易位。该研究项目将重点关注 MLL 易位的功能分析，重点关注 MLL-CBP 易位。 MLL-CBP 被克隆为 t(11;16) (q23;p13) 患者中存在的 MLL 融合体。除一名例外外，这些患者患有与治疗相关的白血病，其中很大一部分患有 t-MDS。我们最近开发了用于 MLL-CBP 融合的体外和体内分析的小鼠模型系统。该项目涉及的研究进一步描绘了 CBP 对融合蛋白贡献的关键功能，确定结构域交换对白血病和白血病前期表型的功能影响，并确定 MLL-CBP 融合对造血细胞谱系定型和存活的影响。