Treatment strategy with PU.1 induction in multiple myeloma and Hodgkin lymphoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461427
• 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: Okuno Yutaka 熊本大学, 大学院生命科学研究部(医), 准教授 (80363539)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: PU.1 / tumor suppressor / 悪性リンパ腫 / 多発性骨髄腫 / IRF4 / IRF7 / IFNβ / 細胞死

Outline of Final Research Achievements

We generated conditional knockout of PU.1 by crossing Cγ1-Cre and PU.1-loxP mice. 75% of the aged knockout mice emerged diffuse large B cell lymphoma, indicating that PU.1 acts as tumor suppressor in B cells.
PU.1 expression induces cell cycle arrest and apoptosis in myeloma cells. We uncovered that PU.1 binds to IRF4 promoter and suppresses IRF4 expression. It was previously reported that IRF4 suppresses IRF7 expression by direct binding to its promoter. Indeed, we found that decreased IRF4 expression subsequently induces IRF7 expression that induces IFNβ expression. IFNβ is expressed in myeloma cells after PU.1 expression and knockdown of IFNβ partially prevent myeloma cells from apoptosis. In conclusion, PU.1 induces apoptosis in myeloma cells by suppression of IRF4 expression and subsequent up-regulation of IRF7 and IFNβ.

Free Research Field

血液内科学