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2021 Fiscal Year Final Research Report

Elucidation for novel target of aggressive B cell lymphoma by whole genome in vivo CRISPR/Cas9 screening

Research Project

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Project/Area Number 20K22854
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Mizutani Shinsuke  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40883088)

Project Period (FY) 2020-09-11 – 2022-03-31
KeywordsCRISPR/Cas9 / MYC / 悪性リンパ腫 / がん抑制遺伝子
Outline of Final Research Achievements

In this study, we performed a comprehensive genome-editing in vivo knockout screening using Eμ-MYC mouse model known to induce highly aggressive B cell lymphoma (BCL). We aimed to identify novel tumor suppressor genes whose deletion forms ultra-high-risk BCLs in concert with MYC overexpression. As a result, two genes on the same pathway were identified as novel tumor suppressor genes (designated genes X and Y for the sake of confidentiality), which were confirmed by in vivo validation experiments. We were also able to confirm their prognostic impact in clinical samples.

Free Research Field

血液内科

Academic Significance and Societal Importance of the Research Achievements

悪性リンパ腫は造血器腫瘍において最も高頻度な疾患群であり、高齢化社会において増加の一途にある。なかでもBCLはその大部分を占めるが、近年の免疫化学療法の発展により、BCLの長期治療成績は著明に改善した。しかしながら、超高リスク病態の形成を機能的観点において司る真の責任分子異常は未だに不明である。本研究で同定した新規がん抑制遺伝子は、高度難治BCL治療における新たな標的分子候補となり、新規治療戦略の開発への発展が期待できる。また、臨床プロファイルとの相関を検討することにより、診断と治療における新たなバイオマーカー確立への応用も期待でき、高度難治BCL治療戦略の大きな発展につながる。

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Published: 2023-01-30  

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