携带MLL-AF9的急性髓系白血病（AML）侵袭性强、预后差。白血病干细胞（LSC）的干性维持是疾病复发的根源，寻找其干预靶点具有重要的科学意义。我们前期研究发现：①SKIDA1在携带MLL-AF9的AML中表达增高且与预后呈负相关。②MLL-AF9直接结合SKIDA1基因，通过增加H3K79me2修饰激活其转录。③SKIDA1敲低可上调PRC2靶基因CDKN2A和CDKN2B转录，降低MLL-AF9细胞株克隆形成能力，延缓MLL-AF9小鼠发病。因此我们提出假说：SKIDA1可能通过PRC2介导的抑癌基因沉默调节MLL-AF9 LSC的维持。本课题拟利用临床样本和条件性敲除小鼠，在分子、细胞和动物水平研究SKIDA1在MLL-AF9 LSC维持中的作用及机制，为该类疾病的治疗提供新思路和潜在靶点。

Acute myeloid leukemia (AML) with MLL-AF9 is an aggressive disease with poor prognosis. It is of great importance to seek ideal target to interfere with the maintenance of leukemic stem cell (LSC), which is the origin of relapse. In our previous study, we found that increased expression of SKIDA1 was correlated with poor prognosis in AML with MLL-AF9. Moreover, MLL-AF9 could directly bind to SKIDA1 to activate its transcription by increasing H3K79me2 occupancy. Further experiments showed that knockdown of SKIDA1 could up-regulate the transcription of PRC2 target genes CDKN2A and CDKN2B, reduce the colony-forming ability of MLL-AF9 cell line, and delay the pathogenesis of MLL-AF9 mice. We therefore hypothesize that SKIDA1 probably regulate the maintenance of MLL-AF9 LSC through PRC2-mediated silencing of tumor suppressor genes. We aim to use clinical samples and conditional knockout mice to study the role and molecular mechanism of SKIDA1 in the maintenance of MLL-AF9 LSC at the molecular, cellular, and animal levels, so as to provide new ideas and potential therapeutic targets for the treatment of such diseases.