Elucidation of molecular pathogenesis and therapeutic targets for refractory hematological malignancies

在这项研究中，我们证明了Evi-1转录的表观遗传调控对其致白血病能力至关重要。我们还揭示了新的分子机制，通过这种机制，AML 1的功能丧失促进白血病发生，使用我们的AML 1条件性敲除小鼠。此外，使用新产生的Evi-1条件性敲除小鼠和Evi-1-ires-GFP敲入小鼠，我们证明了Evi-1和造血干细胞或白血病干细胞表型之间的独特关系。这些结果为难治性恶性血液病的分子靶向治疗提供了基础。

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.