Targeting lysine acetyltransferase TIP60 in hematological malignancies

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08418
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyushu University
• Principal Investigator: Numata Akihiko 九州大学, 医学研究院, 共同研究員 (60423563)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: TIP60 / AML

Outline of Final Research Achievements

In hematological malignancies, the high expression of MYC, a critical transcription factor for proliferation should be correlated with clinical outcomes of the patients. Recent studies have identified TIP60 as a major co-activator of MYC. In the current study, we sought to test whether inhibition of TIP60 could have a therapeutic potential against human hematological malignancies. We first performed ChIP-seq analysis to clarify the TIP60 distribution. We further tried to delete TIP60 in human cell lines by CRISPR/CAS9 system targeting KAT5 gene which encoded human TIP60. However, we could not establish appropriate TIP60-knocked out cell lines.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行により、ヒト造血器腫瘍におけるTIP60分布に関する基礎的なデータが得られた。現在、in silicoでの解析を継続しており、腫瘍細胞の種類ごとにTIP60が制御する重要な遺伝子群が異なっている可能性を見出した。今後はこのデータを元に疾患ごとに治療標的となりうるTIP60の標的遺伝子の同定に取り組む予定であり、本研究の果たした基盤的研究としての役割は大きいものであったと考える。