恶性血液病中染色体del(11q)的共同缺失区、该区域内相关基因的鉴定及功能研究

del(11q)可见于慢性淋巴细胞白血病（CLL）、骨髓增生异常综合症（MDS）、急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）等。目前关于del(11q)的共同缺失区域的定位不完全、缺失区的相关基因亦未明确。前期通过常规核型和荧光原位杂交（FISH）技术，自6000余例初诊CLL、AML、MDS、ALL患者中，筛选出伴del(11q)的病例102例，并进行了初步的断裂点定位。本研究拟在前期基础上，①采用FISH、比较基因组学，检测恶性血液病患者del(11q)的共同缺失区，探讨del(11q)在评判恶性血液病预后中的意义；②用cDNA芯片和定量RT-PCR方法检测候选基因的表达；③运用基因转染及RNAi技术进行候选基因的功能研究。通过研究阐明del(11q)的临床特点、生物学特征、致病机制、预后意义及寻找新的治疗靶点提供理论和实验依据。

Deletion on the long arm of chromosome 11 (del (11q)) has been frequently observed in B-cell chronic lymphocytic leukemia (CLL), myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and acute lymphoblastic leukaemia (ALL). The identification of the common deleted regions has not been completed and the related genes are not clear to date. We found 102 cases with del(11q) in 6000 cases de novo CLL, AML, MDS and ALL patients use conventional cytogenetic analysis and fluorescence in situ hybridization (FISH). The different breakpoints of chromosome 11 were identified. In this study, we intend to identify the common deleted regions using FISH and comparative genomic hybridization (CGH) and to discuss prognostic significance in hematological malignancies patients with del(11q); Secondly, detecting the expression of the candidate genes in common deleted regions using cDNA chip and RT-PCR; Thirdly, exploring the function of the candidate genes using gene transfection and RNAi. By conducting this study, we intend to establish new theoretical bases for the clinical and biological characterization, pathogenesis and prognostic significance of hematological malignancies and also the role of del(11q) in their, to provide new ways for targeting therapy.