Elucidation of the novel epigenetic mechanism promoting a subset of hematologic malignancies

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07346
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Kindai University
• Principal Investigator: UEDA Takeshi 近畿大学, 医学部, 准教授 (60585149)
• Co-Investigator(Kenkyū-buntansha): 金井 昭教 東京大学, 大学院新領域創成科学研究科, 特任准教授 (60549567)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エピジェネティクス

Outline of Final Research Achievements

Our prior work has shown that the histone lysine demethylase KDM4B epigenetically promotes acute myeloid leukemia (AML) associated with chromosomal translocation 8;21 [t(8;21)]. In the present study, we demonstrated that each of the proline-rich region, PHD domain, and Tudor domain of KDM4B is required for proliferation of t(8;21) AML cells, besides the demethylase activity of this protein. Among them, the proline-rich region was found to be essential for the interaction with BRG1-chromatin remodeling enzyme.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究課題では特定の染色体異常を伴う急性骨髄性白血病において、ヒストン脱メチル化酵素KDM4Bが、酵素活性非依存的な細胞増殖効果を担うのに必要なアミノ酸領域を明らかにした。治療標的としてKDM4Bの機能を阻害するために有用な知見が得られた。