Molecular Genetics of CLL

CLL 的分子遗传学

• 批准号: 8068809
• 负责人: CARLO M CROCE
• 金额: $ 58.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8068809
• 关键词: 1 year old; 11q23; 13q14; 14q32; 17p13; Achievement; Age-Years; B-Cell Neoplasm; Characteristics; Chromosome Deletion; Chromosomes, Human, Pair 12; Chronic Lymphocytic Leukemia; Code; Collection; Cytogenetics; DNA Sequence Rearrangement; Development; Diagnosis; Disease; Disease Progression; Etiology; FarGo; Follicular Lymphoma; Gene Chips; Gene Expression; Genes; Genetic; Germ-Line Mutation; Goals; Human; Immunoglobulin Variable Region; In Vitro; Incidence; Individual; Malignant Neoplasms; Mantle Cell Lymphoma; Mature B-Lymphocyte; MicroRNAs; Minority; Molecular; Molecular Genetics; Molecular Profiling; Mutate; Mutation; Older Population; Paper; Pathogenesis; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Physicians; Proteins; Reporting; Research; Role; Scientist; Somatic Mutation; Susceptibility Gene; Time; Tumor Suppressor Genes; ZAP-70 Gene; adult leukemia; in vivo; leukemia; member; mouse model; novel strategies; novel therapeutic intervention; outcome forecast; t(11; 14)(q13; q32); t(14; 18)(q32; q21); variable region gene

During the past four years of support we have made tremendous progress, have achieved the goals o the original proposal and have been able to go far beyond the proposed aims. Among these achievements we were able to develop a mouse model of CLL, to establish the role of the Tcl1/Akt pathway in the pathogenesis of CLL, to discover the role of miR genes in CLL, to dissect the genetics of 6q alterations in CLL with poor prognosis, to discover the ARLTS1 tumor suppressor gene at 13q14 and a germline mutation of this gene that predisposes to a variety of human cancers including CLL, and to develop a miR gene chip to investigate patterns of miR expression in this malignancy. In this renewal application we propose: 1) to continue our studies to dissect the genetics of sporadic and familial CLL; 2) to establish the role of miR genes in sporadic and familial CLL.

在过去的四年中，我们取得了巨大的进步，实现了目标O 最初的提议，已经能够超越拟议的目标。在这些成就中 我们能够开发CLL的鼠标模型，以建立TCL1/AKT途径的作用 CLL的发病机理，发现miR基因在CLL中的作用，以剖析6Q改变的遗传学 预后不良的Cll，发现13 Q14的ARLTS1肿瘤抑制基因和种系突变 这种基因易于包括CLL在内的各种人类癌症，并开发MiR基因芯片 在这种恶性肿瘤中研究miR表达的模式。 在此续签应用中，我们建议： 1）继续我们的研究以剖析零星和家族性CLL的遗传学； 2）确定miR基因在零星和家族性CLL中的作用。