Genome editing in human hematopoietic cells for the understanding of leukemogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09478
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kumamoto University
• Principal Investigator: MATSUI HIROTAKA 熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
• Research Collaborator: SHINRIKI Satoru 熊本大学, 大学院生命科学研究部, 准教授 ; NAGAMACHI Akiko 広島大学, 原爆放射線医科学研究所, 助教
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ゲノム編集 / 急性骨髄性白血病 / 骨髄異形成症候群 / DDX41

Outline of Final Research Achievements

To elucidate the pathogenesis of hematopoietic tumors caused by gene mutations or deletions, we applied genome editing for leukemia cell lines and cord blood-derived CD34 positive hematopoietic progenitor cells. In this study, we targeted the DDX41, where germ line as well as somatic mutations are observed at a certain rate, for gene editing. We previously revealed that DDX41 protein plays a role in the processing of pre-ribosomal RNA, however, its physiological function and the role of its mutant for leukemogenesis has not been elucidated so far.
We found that a leukemia cell line that does not express DDX41, established using CRISPR/CAS9 system, showed growth inhibition as compared with control cells. We assume this was caused by the inhibition of ribosome biogenesis, and further studies using these cells are underway.

Free Research Field

血液内科学、分子生物学