Imatinib耐药和复发是慢性粒细胞性白血病(CML)临床治疗的棘手难题，其源头因素是白血病干细胞(LSCs)的持续存在。然而LSCs自我更新的调控机制仍不清楚。前期研究发现CML LSCs中存在特异的超级增强子(SEs)，LSCs的存活和自我更新高度依赖SEs转录复合物的关键组分CDK7激酶，综合分析RNA-Seq和ChIP-Seq结果鉴定了潜在促进CMLLSCs自我更新的SEs相关基因。据此我们提出科学假说：靶向CDK7抑制SEs驱动基因的过度转录进而抑制LSCs的存活和自我更新。本课题拟进一步系统研究靶向CDK7抑制CML LSCs自我更新的作用；阐明SEs相关基因促进CML LSCs自我更新的作用及其机制；明确CDK7抑制剂THZ1抑制SEs相关基因的转录选择性清除CML LSCs。本课题从SEs的角度阐明LSCs自我更新调控的新机制，为靶向清除LSCs提供了一种新的治疗策略。

Imatinib (IM) resistance and disease relapse remain troublesome problems in clinical treatment of patients with chronic myelogenous leukemia (CML). Leukemia stem cells (LSCs) are considered as sources of IM resistance in CML, however, the nature of LSCs-specific pathways remains poorly understand. In the preliminary study, we characterized the super-enhancers (SEs) landscape in CML LSCs; found that the self-renewal and survival of CML LSCs were highly addicted to CDK7 kinase which is the key component of SEs transcriptional machinery; identified potential SEs-associated oncogenes in CML LSCs by performing an integrative analysis of ChIP-seq and RNA-seq. These findings prompted us to hypothesize that disruption of hyper-transcription of SEs-associated gene by targeting CDK7 efficiently eradiated the CML LSCs. The present study is aimed at systematically studying the role of CDK7 in sustaining the self-renewal of CML LSCs by using BCR-ABL-driven CML mouse model; elucidating that the maintenance of self-renewal and survival of CML LSCs was highly addicted to SEs-associated gene(s); observing the eradication effect of disruption SEs-associated transcripts by CDK7 inhibitor THZ1 on CML LSCs. Taken together, this is the first time to establish the SEs landscape in LSCs, and perturbed the cellular transcriptional machinery required for SEs may be a promising strategy to clear CML LSCs.