The molecular basis of limited-stage DLBCL

• Project/Area Number: 21K16262
• 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: University of Tsukuba
• Principal Investigator: Suehara Yasuhito 筑波大学, 附属病院, 病院講師 (90844811)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2021: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 悪性リンパ腫 / オミクス研究 / びまん性大細胞型B細胞リンパ腫 / RNAシーケンス解析 / 全エクソームシーケンス解析 / 病期 / アーカイブデータ

Outline of Research at the Start

びまん性大細胞型B細胞リンパ腫（Diffuse large B-cell lymphoma: DLBCL）において、病期は確立した予後規定因子である。病期を一つの表現型と捉えた際に、限局期あるいは進行期となりやすい分子基盤の存在は十分に検討されていない。アーカイブデータを利用し、限局期DLBCLに特徴的なSignature（仮にLimited-stage signature, LSとする）を探求し、LSの有無と予後の違い、既知のゲノム異常サブタイプとの対応について検討する。また、LSの喪失が腫瘍進展の経路として、治療標的になりうるか検討する。

Outline of Final Research Achievements

The stage is a well-established prognostic factor in diffuse large B-cell lymphoma (DLBCL). The molecular basis harboring limited-stage or advanced disease has not been adequately explored when considering stage as a phenotype. We aimed to identify limited-stage signatures (LSs) characteristic of limited-stage DLBCL, investigate the relationship between the presence or absence of LSs and prognosis, and their correspondence with known DLBCL genetic/transcriptomic subtypes. We re-analyzed 1000 whole exome sequencing (WES) and 775 RNA sequencing (RNA-seq) datasets from EGAS00001002606.

Academic Significance and Societal Importance of the Research Achievements

限局期DLBCLは全体の約30%を占め、PET-CTによる評価や一部の若年者では生存率を損なうことなく治療強度を減弱できるエビデンスが出てきている。一方で、5-10%程度は初回治療で奏効が得られない、あるいは再発をする。まだ成果が得られていないが、limited-stage signatureが限局期DLBCLの中での層別化に寄与できれば、より適切な治療戦略に繋がると考えられる。

Research Products

• [Journal Article] Triple-negative Thrombocythemia and Subsequent Acute Lymphoblastic Leukemia with Additional Somatic Mutations (2023)
  • Author(s): Tsuboi Y, Sakamoto T, Makishima K, Suehara Y, Hattori K, Kurita N, Yokoyama Y, Kato T, Nishikii H, Obara N, Matsumura F, Matsuoka R, Chiba S, Sakata-Yanagimoto M.
  • Journal Title: Internal Medicine Volume: 62 Issue: 10 Pages: 1527-1530
  • DOI: 10.2169/internalmedicine.0269-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-05-15
  • Peer Reviewed / Open Access
• [Journal Article] Cardiac Tamponade as a Recurrence of Angioimmunoblastic T-Cell Lymphoma with the Detection of a p.Gly17Val RHOA Mutation in the Pericardial Effusion (2023)
  • Author(s): Tsuboi Yuri、Iimura Yumoe、Matsumura Fumiaki、Nanmoku Toru、Suma Sakurako、Matsuoka Ryota、、、、、Sato Kimi、Maruyama Yumiko、Sakamoto Tatsuhiro、Yokoyama Yasuhisa、Kato Takayasu、Kurita Naoki、Nishikii Hidekazu、Obara Naoshi、Ieda Masaki、Chiba Shigeru、Sakata-Yanagimoto Mamiko
  • Journal Title: Internal Medicine Volume: 62 Issue: 4 Pages: 595-600
  • DOI: 10.2169/internalmedicine.9248-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-02-15
  • Peer Reviewed / Open Access
• [Journal Article] Lymphoplasmacytic lymphoma accompanied by severe myelofibrosis (2023)
  • Author(s): 宝田亜矢子, 百瀬春佳, 栗田尚樹, 松岡亮太, 中村直哉, 坂本竜弘, 加藤貴康, 服部圭一朗, 末原泰人, 横山泰久, 錦井秀和, 丸山ゆみ子, 小原 直, 千葉 滋, 坂田（柳元）麻実子
  • Journal Title: Rinsho Ketsueki Volume: 64 Issue: 1 Pages: 54-59
  • DOI: 10.11406/rinketsu.64.54
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Hematopoietic recovery by <i>ASXL1</i>-mutated clones after immune suppressive therapy in a patient with severe aplastic anemia (2023)
  • Author(s): 清水 百萌、服部 圭一朗、丸山 ゆみ子、南谷 泰仁、小川 誠司、坂田（柳元） 麻実子、千葉 滋、小原 直、錦井 秀和、飯塚 正、松岡 亮太、栗田 尚樹、坂本 竜弘、横山 泰久、加藤 貴康、末原 泰人
  • Journal Title: Rinsho Ketsueki Volume: 64 Issue: 1 Pages: 49-53
  • DOI: 10.11406/rinketsu.64.49
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Clonal heamatopoiesis and associated cardiovascular diseases (2023)
  • Author(s): Tajiri Kazuko、Suehara Yasuhito、Suzuki Toshio、Sekine Ikuo
  • Journal Title: Japanese Journal of Clinical Oncology Volume: 53 Issue: 3 Pages: 187-194
  • DOI: 10.1093/jjco/hyac210
  • Peer Reviewed
• [Journal Article] Acute myeloid leukemia harboring <i>NUP98::DDX10</i> (2022)
  • Author(s): 栗田 尚樹、坪井 宥璃、小原 直、錦井 秀和、坂田（柳元） 麻実子、千葉 滋、加藤 貴康、南木 融、丸山 ゆみ子、末原 泰人、服部 圭一朗、坂本 竜弘、横山 泰久、吉田 近思
  • Journal Title: Rinsho Ketsueki Volume: 63 Issue: 10 Pages: 1397-1401
  • DOI: 10.11406/rinketsu.63.1397
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Clonal germinal center B cells function as a niche for T-cell lymphoma (2022)
  • Author(s): Fujisawa M, Nguyen TB, Abe Y , Suehara Y, Fukumoto K, Suma S, Makashima K, Kaneko C, Nguyen YTM, Usuki K, Narita K, Matsue K, Nakamura N, Ishikawa S, Miura F, Ito T, Suzuki A, Suzuki Y, Mizuno S, Takahashi S, Chiba S, and Sakata-Yanigimoto M
  • Journal Title: Blood Volume: 140 (18) Issue: 18 Pages: 1937-1950
  • DOI: 10.1182/blood.2022015451
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pathogenesis and therapeutic advances of peripheral T-cell lymphoma (2022)
  • Author(s): 坂田（柳元） 麻実子、末原 泰人
  • Journal Title: Rinsho Ketsueki Volume: 63 Issue: 6 Pages: 626-634
  • DOI: 10.11406/rinketsu.63.626
  • ISSN: 0485-1439, 1882-0824
• [Journal Article] A case of NASH with genetic predisposition successfully treated with an SGLT2 inhibitor: a possible involvement of mitochondrial dysfunction. (2022)
  • Author(s): Nakajima R, Sekiya M, Furuta Y, Miyamoto T, Sato M, Fukuda K, et, al.
  • Journal Title: Endocrinol Diabetes Metab Case Rep. Volume: 22 Pages: 0368-0368
  • DOI: 10.1530/edm-22-0368
  • Peer Reviewed / Open Access
• [Presentation] Genetic subtypes of angioimmunoblastic T-cell lymphoma are associated with distinct outcomes (2022)
  • Author(s): Suehara Y, Sakamoto K, Fujisawa M, Fukumoto K, Abe Y, Makishima K, Suma S, Sakamoto T, Hattori K, Maruyama Y, Kato T, Kurita N, Yokoyama Y, Nishikii H, Obara N, Sugio T, Kato K, Akashi K, Matsue K, Narita K, Takeuchi K, Nakamura N, Chiba K, Shiraishi Y, Miyano S, Ogawa S, Chiba S, Sakata-Yanagimoto M
  • Organizer: 第84回日本血液学会学術集会