The role of the non-coding RNA PVT1 in malignant lymphoma

• Project/Area Number: 19K17839
• 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: Wakayama Medical University
• Principal Investigator: Hosoi Hiroki 和歌山県立医科大学, 医学部, 助教 (00646036)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: PVT1 / 8q24転座 / long non-coding RNA / microRNA / micro RNA / 悪性リンパ腫 / double hit lymphoma

Outline of Research at the Start

悪性リンパ腫患者数は高齢化とともに増加傾向で、副作用の少ない分子標的治療薬の開発につながる悪性リンパ腫発症機序解明は重要である。8q24転座を有する悪性リンパ腫の中には極めて予後不良な疾患群があり、その中には8q24転座点がガン遺伝子MYCの下流にあるPVT1内に存在する症例がある。PVT1は長鎖非コードRNAであり、腫瘍化におけるPVT1の役割は不明である。本研究では悪性リンパ腫発症におけるPVT1領域の役割を明らかにし、新規治療へつなげることを目的とする。

Outline of Final Research Achievements

The role of PVT1, which is a long non-coding RNA gene located downstream of the MYC gene, was examined. The expression of MYC was higher in cell lines with breakpoints in the PVT1 gene than in cell lines with breakpoints around the MYC gene. The expression pattern of microRNAs encoded by PVT1 was not associated with the location of breakpoints in the 8q24 region. A BET bromodomain inhibitor, JQ1, suppressed the growth of B-cell lines with 8q24 breakpoints through the reduction of MYC and PVT1 5’ expression. The inhibition of PVT1 5’ and miR1204 expression did not lead to the suppression of B-cell proliferation.

Academic Significance and Societal Importance of the Research Achievements

8q24転座を有する悪性リンパ腫の中には予後が悪い一群があり、悪性リンパ腫に対する新たな治療法の開発が望まれる。8q24にはガン遺伝子であるMYCが存在するが、MYCは正常細胞でも重要な機能を有しているためMYCを標的とした薬剤は開発が難しい可能性がある。近年、lncRNAをターゲットとした核酸医薬開発への注目が高まっており、PVT1は治療標的になり得ると考えている。本研究は悪性リンパ腫発症におけるPVT1の役割を考える上で基礎的な知見を与える。

Research Products

• [Journal Article] Composite Epstein-Barr Virus-associated T-lymphoblastic and Peripheral T-cell Lymphomas: A Clonal Study (2021)
  • Author(s): Hosoi Hiroki、Mushino Toshiki、Nakashima Kazutaka、Kuriyama Kodai、Tamura Shinobu、Murata Shogo、Imadome Ken-Ichi、Ohshima Koichi、Sonoki Takashi
  • Journal Title: Internal Medicine Volume: 60 Issue: 13 Pages: 2119-2123
  • DOI: 10.2169/internalmedicine.6572-20
  • NAID: 130008060437
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-07-01
  • Peer Reviewed / Open Access
• [Journal Article] 右房内腫瘤を契機に診断に至ったErdheim-Chester病 (2021)
  • Author(s): 武田 里美、栩野 祐一、山下 友佑、細井 裕樹、蒸野 寿紀、西川 彰則、田村 志宣、園木 孝志、村田 祥吾、太根 美聡、吉田 菊晃、岩元 竜太、割栢 健史、榊 絢朱、横矢 悠馬、田中 顕
  • Journal Title: 臨床血液 Volume: 62 Pages: 91-93
  • NAID: 130007995472
  • Peer Reviewed
• [Journal Article] Super-enhancers for RUNX3 are required for cell proliferation in EBV-infected B cell lines (2021)
  • Author(s): Hosoi Hiroki、Niibori-Nambu Akiko、Nah Giselle Sek Suan、Bahirvani Avinash Govind、Mok Michelle Meng Huang、Sanda Takaomi、Kumar Alan Prem、Tenen Daniel G.、Ito Yoshiaki、Sonoki Takashi、Osato Motomi
  • Journal Title: Gene Volume: 774 Pages: 145421-145421
  • DOI: 10.1016/j.gene.2021.145421
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dose-adjusted high-dose chemotherapy with autologous stem cell transplantation for elderly (70 years old) lymphoma patients (2021)
  • Author(s): Hosoi Hiroki、Murata Shogo、Mushino Toshiki、Tamura Shinobu、Sonoki Takashi
  • Journal Title: Annals of Hematology Volume: - Issue: 1 Pages: 205-207
  • DOI: 10.1007/s00277-020-04373-z
  • Peer Reviewed
• [Journal Article] Targeting Adaptive IRE1α Signaling and PLK2 in Multiple Myeloma: Possible Anti-Tumor Mechanisms of KIRA8 and Nilotinib. (2020)
  • Author(s): Yamashita Y, Morita S, Hosoi H, Kobata H, Kishimoto S, Ishibashi T, Mishima H, Kinoshita A, Backes BJ, Yoshiura KI, Papa FR, Sonoki T, Tamura S
  • Journal Title: Int J Mol Sci. Volume: Aug 31;21(17) Issue: 17 Pages: 6314-6314
  • DOI: 10.3390/ijms21176314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Susceptibility of patients receiving chemotherapy for haematological malignancies to scabies (2020)
  • Author(s): Hosoi H.、Nishikawa S.、Kida Y.、Kishi T.、Murata S.、Iwamoto M.、Toyoda Y.、Yamada Y.、Ikeda T.、Sonoki T.
  • Journal Title: Journal of Hospital Infection Volume: 106 Issue: 3 Pages: 594-599
  • DOI: 10.1016/j.jhin.2020.08.021
  • Peer Reviewed
• [Journal Article] Eosinophilia during letermovir treatment after allogeneic hematopoietic stem cell transplantation (2020)
  • Author(s): Hosoi Hiroki、Murata Shogo、Mushino Toshiki、Nishikawa Akinori、Sonoki Takashi
  • Journal Title: Annals of Hematology Volume: 99 Issue: 10 Pages: 2453-2454
  • DOI: 10.1007/s00277-020-04226-9
  • Peer Reviewed
• [Journal Article] Two Episodes of Transfusion-related Acute Lung Injury (TRALI) Occurring within a Short Period (2020)
  • Author(s): Akagi Yuina、Murata Shogo、Yamashita Yusuke、Tanaka Ken、Hiroi Takayuki、Mushino Toshiki、Hosoi Hiroki、Nishikawa Akinori、Tamura Shinobu、Sonoki Takashi
  • Journal Title: Internal Medicine Volume: 59 Issue: 20 Pages: 2577-2581
  • DOI: 10.2169/internalmedicine.4700-20
  • NAID: 130007926297
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] レテルモビル投与下の同種造血幹細胞移植後好酸球増多 (2021)
  • Author(s): 細井裕樹、村田祥吾、蒸野寿紀、田畑翔太朗、松山依子、吉田菊晃、赤木佑衣奈、小浴秀樹、田中顕、弘井孝幸、山下友佑、西川彰則、田村志宣、園木孝志
  • Organizer: 第43回日本造血細胞移植学会総会
• [Presentation] 70歳以上の悪性リンパ腫患者に対する投与量調整大量化学療法併用の自家移植 (2021)
  • Author(s): 細井裕樹、村田祥吾、蒸野寿紀、西川彰則、田村志宣、園木孝志
  • Organizer: 第48回和歌山悪性腫瘍研究会
• [Presentation] Nivolumab投与後の同種移植で重症GVHDを生じたホジキンリンパ腫の一例 (2020)
  • Author(s): 細井裕樹、赤木佑衣奈、田村志宣、田中顕、大岩健洋、蒸野寿紀、村田祥吾、西川彰則、園木孝志
  • Organizer: 第42回日本造血細胞移植学会総会
• [Presentation] Safety and efficacy of dose adjusted high-dose chemotherapy with ASCT for the elderly with lymphoma (2020)
  • Author(s): Hiroki Hosoi, Shogo Murata, Kikuaki Yoshida, Ken Tanaka, Takayuki Hiroki, Masaya Morimoto, Takehiro Oiwa, Yusuke Yamashita, Toshiki Mushino, Akinori Nishikawa, Shinobu Tamura, Takashi Sonoki
  • Organizer: 第82回日本血液学会学術集会