Development of a novel therapeutic strategy targeting MYC for leukemia with monosomy 7

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16241
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Matsuda Kensuke 東京大学, 医学部附属病院, 助教 (40880175)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: モノソミー7 / 合成致死 / MYC / エピゲノム

Outline of Final Research Achievements

The aim of this study is to develop MYC-targeted therapies for leukemias with monosomy of chromosome 7 (monosomy 7). Our group identified several target genes in a therapeutic target screen based on the concept of synthetic lethality, suggesting that they may exert their effects by downregulating MYC. Using leukemia cell lines and patient samples, we confirmed that MYC inhibitory therapy inhibited the growth of monosomy 7 leukemia cells. In addition, we found that MYC inhibition contribute to a lower tumor progression and mouse survival in an immunodeficient mouse model. MYC is required for survival. MYC is an essential gene for cell function, but its expression level was suppressed to a lower level in monosomy 7 leukemia, which may induce the vulnerability to MYC inhibitory therapy.

Free Research Field

血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究では、難治性であるモノソミー7を伴う白血病の新しい脆弱性を明らかにした。加えて、本研究は、染色体欠失という事象に対して、新しい治療標的探索アプローチを提示する可能性がある。本研究が発展し、難治性白血病に対する新しい治療法の開発及び治療成績向上が期待される。