2018 Fiscal Year Final Research Report

Relationship between NfkB signaling and epigeneteic signaling in malignant lymphoma.

Research Project

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Project/Area Number	16K09865
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Hematology
Research Institution	International University of Health and Welfare (2017-2018) National Cancer Center Japan (2016)
Principal Investigator	Kobayashi Yukio 国際医療福祉大学, 医学部, 教授 (50240734)
Co-Investigator(Kenkyū-buntansha)	野本順子国際医療福祉大学, 医学部ゲノム医学研究所, 助手 (30601322) 福原傑国立研究開発法人国立がん研究センター, 中央病院, 医員 (70445295) 棟方理国立研究開発法人国立がん研究センター, 中央病院, 医員 (80601319) 前島亜希子国立研究開発法人国立がん研究センター, 中央病院, 医員 (90342906)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	BCR / NFkB / target sequence
Outline of Final Research Achievements	We performed target sequences of 18 pairs of primary and relapsed DLBCL cases. Among them, 9 pairs had common mutations in MYD88, CD79B, RHOA, TNFRSF14, PIM,MLL2, CREBBP, PRDM1, MEF2B genes.Some common characteristics might be shared in a subgroup of pts with limited-stage DLBCL who developed LR; they had non-GCB type, mutation in both or either of CD79B and MYD88 and specific extranodal diseases. Especially, at least four pts were considered to have MCD type with co-mutation of CD79B and MYD88. The mechanisms of localized relapse(LR) were considered heterogeneous. In addition to the well-known mechanism of relapse with indolent BCL components, acquiring functions associated with immune evasion were speculated in limited pts. Immunodeficiency by aging might also be associated with LR because median age at LR was 71 years, relatively old. Other mechanisms of LR, such as gene alteration involving other than PD-L1 must exist although not revealed in our study.
Free Research Field	血液腫瘍学
Academic Significance and Societal Importance of the Research Achievements	悪性リンパ腫の検体で実用上、問題なく遺伝子検査ができる系を確立した。悪性リンパ腫では、個々の遺伝子変異に応じた治療薬が１：１で見つかるわけではない。しかし、悪性リンパ腫の発症に関する遺伝子群（パスウェイ）がわかってきており、そのパスウェイごとには、阻害剤が発見されてきている。この研究は、将来的には、個別化治療の元になり、より副作用がない、より効果のある治療薬が選択できる元となると考えられる。事実、限局性の病変で、長年の後に再発している例では、将来はそのパスウェイに応じた治療薬で維持療法を行うようになるかもしれない。