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Role of CEBPA mutations in RAS-mediated leukemogenesis

Title
Role of CEBPA mutations in RAS-mediated leukemogenesis
Author
이주연
Alternative Author(s)
이주연
Advisor(s)
정희용
Issue Date
2021. 2
Publisher
한양대학교
Degree
Master
Abstract
Oncogenic RAS mutations are critical in inducing several forms of human myeloid leukemia. Previous study has shown that NRASG12D alone is not sufficient to promote malignant tumors. Therefore, I screened several oncogenes (C/EBPα p30, IRX3, and CBFβ-MYH11) that have been known to affect myeloid differentiation for collaboration with NRASG12D in leukemia induction. I confirmed synergistic effect of C/EBPα p30 and NRASG12D combination in in vitro proliferation assay. The transcriptions factor CEBPA (CCAAT/enhancer binding protein α) is crucial for myeloid differentiation and growth arrest. Mutations in the CEBPA genes are found in about 10% of acute myeloid leukemia (AML) patients, and they are mostly biallelic CEBPA mutations. One mutation leads to the frame-shifted mutation at N-terminus (C/EBPα p30) and the other leads to C-terminal point mutations at the basic leucine zipper domain (C/EBPα BRM). In this study, I investigated three forms of C/EBPα mutations and their combinations for their ability of inducing leukemia in collaboration with NRASG12D. The three C/EBPα mutant forms used in this experiment are p30, BRM2 and dual mutation of p30 and BRM. Among these C/EBPα mutants, p30-BRM dual mutant form, having both C-terminal and N-terminal mutation in a single cistron, showed most potent synergistic effect with NRASG12D. With this system, I analyzed the effect of BRM2 mutation in shifting the transcriptome of leukemic cells in the presence of NRASG12D and I believe the results from this study will offer unique opportunity of understanding the mechanism of the appearance of biallelic C/EBPα mutation in myeloid leukemia patients.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/159085http://hanyang.dcollection.net/common/orgView/200000485708
Appears in Collections:
GRADUATE SCHOOL OF BIOMEDICAL SCIENCE AND ENGINEERING[S](의생명공학전문대학원) > BIOMEDICAL SCIENCE(의생명과학과) > Theses (Master)
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