MLL-AF4阳性急性淋巴细胞白血病是一种难治型急性白血病，患者携带t(4; 11)(q21; q23)易位（产生MLL-AF4融合蛋白），在成人急淋中为第二大常见染色体异常，预后极差，是治疗的难点，亟需从分子机制揭示发病机理。MLL-AF4融合蛋白对该类白血病起到至关重要的作用，我们研究组发现人类miR-143是一个抑癌基因，它可以特异性下调MLL-AF4融合蛋白，而且在MLL-AF4阳性急性淋巴细胞白血病中出现特异性高甲基化及低表达，从而加剧白血病细胞恶性增殖，在白血病发病中发挥重要作用。在此基础上，我们拟进一步深入分析MLL-AF4原癌基因与miR-143如何互相调控，形成调控环路导致白血病难治复发的分子机制，揭示MLL-AF4原癌基因与甲基化及microRNA在遗传学及表观遗传学调控网络中相互作用的机理，并探讨去甲基化药物作为新的临床治疗手段的可行性。

MLL-AF4 acute lymphoblastic leukemia patients harbor the translocation of t(4;11)(q21;q23), which results in the formation of leukemic MLL-AF4 fusion protein. t(4;11)(q21;q23) is the second most popular chromosomal transclocation in adults acute lymphoblastic leukemia. MLL-AF4 acute lymphoblastic leukemia patients have a notoriously poor prognosis. Most of patients still died even after stem cell translpantation. This raises the question of how this disease can evolve so quickly. But the detail mechanism of this disease is not clear, also short of effective theraputic methods. We found that miR-143 can target MLL-AF4 fusion protein, which play important role in MLL-AF4 leukemia, and was repressed by hypermethylation only in MLL-AF4 positive leukemia, but not in healthy people and MLL-AF4 negative leukemia. These results were published in the journal of Oncogene. Next, we want to deeply explore the genetic and epigenetics regulatory mechanism of methylation, microRNA and MLL-AF4 oncogene involved in refractory leukemia. In addition, we also want to systematically characterize the promise of demethylating drugs and miR-143 as a candidate for the development of new treatment.