Pb1801: mycn is required for maintaining an oncogenic characteristics of leukemia cells in acute myeloid leukemia

Topic: 3. Acute myeloid leukemia - Biology & Translational Research Background: MYCN is a member of the MYC proto-oncogene family that also includes MYC and MYCL. Overexpression of MYCN is frequent in several solid cancers and associated with poor prognosis. However, the role of MYCN in acute myeloid leukemia (AML) remains poorly understood. Aims: To investigate the mechanism of MYCN in maintenance of malignant characteristic of leukemia cells. Methods: The expression of MYC family was analyzed in 542 AML patients, 76 chronic myeloid leukemia (CML) patients and 74 non-leukemia/healthy controls from Microarray Innovations in Leukemia (MILE) study. Lentivirus-mediated MYCN knockdown was performed to investigate its biological function in leukemia cell lines. The mechanism of MYCN in leukemia development was investigated by functional experiments. Results: We found that MYCN, not MYC or MYCL, was up-regulated in the AML patients compared with CML or non-leukemia controls. In vitro experiments, knockdown of MYCN impaired growth capacity, elevated autonomously cell apoptosis and increased apoptosis sensitivity to cytotoxic agent. Gene microarray and bioinformatic analysis suggested that MYCN plays a critical role in transcription regulation and apoptosis pathway. Correlation analysis and functional experiments revealed that MSI2 is a target of MYCN. Knockdown of MYCN inhibited the expression of MSI2. Mechanistically, MYCN could directly bind at the promoter of MSI2 and promote its transcription. Summary/Conclusion: MYCN oncogene contributes to the malignant characteristics of leukemia cells through activation of MSI2 in AML. MYCN is required for maintaining an oncogenic characteristics of leukemia cells in acute myeloid leukemia This study was supported by the National Natural Science Foundation of China (Grant No. 81770120 and 81770122) The authors declare no competing financial interests. Keywords: Acute myeloid leukemia, MYC, Oncogene