Elucidation of molecular pathogenesis and therapeutic targets for refractory hematological malignancies

在这项研究中，我们证明了Evi-1对转录的表观遗传调控是其致白血病能力所必需的。我们还利用我们的AML1条件性基因敲除小鼠揭示了AML1功能丧失促进白血病发生的新的分子机制。此外，使用新产生的EVI-1条件基因敲除小鼠和EVI-1-res-GFP敲入小鼠，我们证明了EVI-1与造血干细胞或白血病干细胞的表型之间存在明显的关系。这些结果为开发治疗难治性血液系统恶性肿瘤的新型分子靶向疗法奠定了基础。

In this study, we demonstrated that the epigenetic regulation of transcription by Evi-1 is essential for its leukemogenic capacity. We also revealed the novel molecular mechanisms by which the loss-of-function of AML1 promotes leukemogenesis, using our Aml1 conditional knockout mice. Furthermore, using newly generated Evi-1 conditional knockout mice and Evi-1-ires-GFP knock-in mice, we demonstrated a distinctive relationship between Evi-1 and the phenotype of hematopoietic stem cells or leukemic stem cells. These results provide a foundation to develop novel molecular targeted therapies for refractory hematological malignancies.