t(12;22)(p13;q12)/TEL-MN1融合基因相关白血病的生物学特征及发病机制研究

t(12;22)(p13;q12)是急性白血病中的一种再现性染色体易位，主要形成TEL-MN1融合基因，该类白血病的生物学特征以及TEL-MN1融合蛋白的主要致白血病机制、调控基因等尚不明确。申请人自大宗急性白血病样本中，筛选出一组伴有该异常的白血病病例，初步研究显示该类患者具有独特的临床、形态学、免疫学、遗传学特征。本课题拟将TEL-MN1融合基因通过真核细胞表达载体，转染至NIH-3T3细胞，建立伴有t(12;22)(p13;q12)/TEL-MN1融合基因的细胞株。并以该细胞株和该组患者为研究对象，采用SNP-芯片、基因表达谱芯片、RQ-PCR、基因转染、RNA干扰和模式生物等手段，从体内外两方面揭示该类白血病的临床和生物学特征以及TEL-MN1融合蛋白致白血病的分子机理和靶向调控途径。旨在为阐明此类患者的白血病发病机制、寻找新的治疗靶点、实现个体化治疗提供理论和实验依据。

t(12;22)(p13;q12) is one of recurrent chromosome transloations in acute leukemia, which forms TEL-MN1 fusion gene. While, the biological characteristics of acute leukemia bearing t(12;22)(p13;q12) is not clear, and the leukemogenesis of t(12;22)(p13;q12) is not confirmed. In our previous study, we selected a cohort of patients bearing t(12;22)(p13;q12) in more than 400 cases of acute leukemia. With preliminary study, this cohort of patients displayed unique clinical, morphologic, immunologic, and genetic characteristics. We transfected NIH-3T3 cells with TEL-MN1 fusion gene and set up a cell line harboring t(12;22)(p13;q12)/TEL-MN1. In our present study, we will study this cell line and the cohort of patients with SNP array, gene array, gene transfection, RNA interference and zebra fish model. The study will focus on the clinical and biological characteristics and the leukemogenesis of TEL-MN1. Our study will provide theoretical basis for the leukemogenesis of t(12;22)(p13;q12)/TEL-MN1, which prompt the target therapy and tailored therapy.