The relationship BCR signaling pathway and functional variants of TNFAIP3/A20

• Project/Area Number: 15K21647
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine; Hematology
• Research Institution: International University of Health and Welfare (2018); National Cancer Center Japan (2015-2017)
• Principal Investigator: Nomoto Junko 国際医療福祉大学, 医学部, 助手 (30601322)
• Research Collaborator: Kobayashi Yukio
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: TNFAIP3/A20 / BCRシグナル経路 / ターゲットシークエンス / ABC-DLBCL / BCRシグナル経路阻害剤 / NF-κB / ターゲットシーケンス / イブルチニブ / 血液腫瘍学 / NF-κBシグナル経路 / NF-kB / BCRシグナル / 次世代シークエンス

Outline of Final Research Achievements

We performed target sequence analysis of ABC-type diffuse large-cell B-cell lymphoma (ABC-DLBCL). The genes of BCR signaling pathway downstream of BTK including NF-κB signaling pathway were analyzed. We found genes downstream from BTK, such as CARD11, and more downstream genes of NF-κB signaling pathway including TNFAIP3/A20 were mutated. These result suggested that the treatment of ABC-DLBCL by BTK inhibitor is not universally effective, especially in cases with mutated genes downstream of BTK.

Academic Significance and Societal Importance of the Research Achievements

ABC-DLBCL の治療効果に関与する因子が同定され、それらが診断・治療選択・予後予測に有用であることを明らかにすることは、ABC-DLBCL のみならず、B 細胞性リンパ腫の新たな治療標的や治療法の開発、および診断や病型分類といった個別化医療の基盤となることが期待される。

Research Products

• [Journal Article] Mucosa-associated lymphoid tissue lymphoma with t(11;18)(q21;q21) translocation: long-term follow-up results. (2019)
  • Author(s): Toyoda K, Maeshima AM, Nomoto J, Suzuki T, Yuda S, Yamauchi N, Taniguchi H, Makita S, Fukuhara S, Munakata W, Maruyama D, Tobinai K, Kobayashi Y.
  • Journal Title: Ann Hematol. Volume: - Issue: 7 Pages: 1675-1687
  • DOI: 10.1007/s00277-019-03671-5
  • Peer Reviewed / Open Access
• [Journal Article] Gene Expression Profile Signature of Aggressive Waldenstrom Macroglobulinemia with Chromosome 6q Deletion (2018)
  • Author(s): Sekiguchi, N. Nomoto, J. Nagata, A. Kiyota, M. Fukuda, I. Yamada, K. Takezako, N. Kobayashi, Y.
  • Journal Title: Biomed Res Int Volume: 2018 Pages: 6728128-6728128
  • DOI: 10.1155/2018/6728128
  • Peer Reviewed / Open Access
• [Journal Article] Expression pattern of PD-L1 and PD-L2 in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and gray zone lymphoma (2018)
  • Author(s): Tanaka Yosuke、Maeshima Akiko Miyagi、Nomoto Junko、Makita Shinichi、Fukuhara Suguru、Munakata Wataru、Maruyama Dai、Tobinai Kensei、Kobayashi Yukio
  • Journal Title: European Journal of Haematology Volume: 100 Issue: 5 Pages: 511-517
  • DOI: 10.1111/ejh.13033
  • Peer Reviewed / Open Access
• [Journal Article] Double-Expressor Lymphoma Is Associated with Poor Outcomes after Allogeneic Hematopoietic Cell Transplantation (2018)
  • Author(s): Kawashima, I. Inamoto, Y. Maeshima, A. M. Nomoto, J. Tajima, K. Honda, T. Shichijo, T. Kawajiri, A. Takemura, T. Onishi, A. Ito, A. Tanaka, T. Fuji, S. Kurosawa, S. Kim, S. W. Maruyama, D. Tobinai, K. Kobayashi, Y. Fukuda, T.
  • Journal Title: Biol Blood Marrow Transplant Volume: 24 Issue: 2 Pages: 294-399
  • DOI: 10.1016/j.bbmt.2017.10.013
  • Peer Reviewed / Open Access
• [Journal Article] Partial deletion of the ALK gene in ALK-positive anaplastic large cell lymphoma (2018)
  • Author(s): Fukuhara Suguru、Nomoto Junko、Kim Sung-Won、Taniguchi Hirokazu、Miyagi Maeshima Akiko、Tobinai Kensei、Kobayashi Yukio
  • Journal Title: Hematological Oncology Volume: 36 Issue: 1 Pages: 150-158
  • DOI: 10.1002/hon.2455
  • Peer Reviewed / Open Access
• [Journal Article] FUS-ERG gene fusion in isolated myeloid sarcoma showing uncommon clinical features. (2016)
  • Author(s): Ueda R, Maruyama D, Nomoto J, Maeshima AM, Fukuhara S, Kitahara H, Miyamoto K, Munakata W, Suzuki T, Taniguchi H, Kobayashi Y, Tobinai K.
  • Journal Title: Oxf Med Case Reports. Volume: 1 Issue: 1 Pages: 4-8
  • DOI: 10.1093/omcr/omv070
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological features of classical Hodgkin lymphoma in patients ≧ 40 years old, with special reference to composite cases. (2015)
  • Author(s): Maeshima AM, Taniguchi H, Nomoto J, Makita S, Kitahara H, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K.
  • Journal Title: Jpn J Clin Oncol. Volume: 45 Issue: 10 Pages: 921-8
  • DOI: 10.1093/jjco/hyv101
  • Peer Reviewed / Open Access
• [Journal Article] Intravascular large B-cell lymphoma secondary to lymphoplasmacytic lymphoma: a case report and review of literature with clonality analysis. (2015)
  • Author(s): Tanaka Y, Kobayashi Y, Maeshima AM, Oh SY, Nomoto J, Fukuhara S, Kitahara H, Munakata W, Suzuki T, Maruyama D, Tobinai K.
  • Journal Title: Int J Clin Exp Pathol. Volume: 8 Pages: 3339-43
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] primary refractoryびまん性大細胞型B細胞リンパ腫の臨床病理学的な検討 (2018)
  • Author(s): 鈴木智貴, 丸山大, 前島亜希子, 野本順子, 田島絹子, 伊藤勇太, 八田俊介, 油田さや子, 蒔田真一, 福原傑, 棟方理, 鈴木達也, 谷口浩和, 伊豆津宏二, 小林幸夫, 飛内賢正
  • Organizer: 第65回日本血液学会学術集会
• [Presentation] Genomics of Limited-Stage Diffuse Large B-Cell Lymphoma Developing Late Relapse: Analysis of Gene Alterations in Paired Primary and Late Relapsed Tumors By Target Sequencing (2018)
  • Author(s): Tomotaka Suzuki, Suguru Fukuhara, Junko Nomoto, Satoshi Yamashita, Akiko Miyagi Maeshima, Yuta Ito, Shunsuke Hatta, Sayako Yuda, Shinichi Makita, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Hirokazu Taniguchi, Toshikazu Ushijima, Koji Izutsu, Kensei Tobinai, and Yukio Kobayashi,MD.
  • Organizer: 60th American Society of Hematology Annual Meeting & Exposition
  • Int'l Joint Research
• [Presentation] Akihisa Kawajiri, Dai Maruyama, Akiko Miyagi Maeshima, Junko Nomoto, Shin-ichi Makita, Hideaki Kitahara, Ken-ichi Miyamoto, Suguru Fukuhara, Tatsuya Suzuki, Wataru Munakata, Kinuko Tajima, Jun Itami, Hirokazu Taniguchi, Yukio Kobayashi, Kensei Tobinai. (2015)
  • Author(s): The impact of concurrent expression of MYC and BCL2 on outcomes of localized Primary Gastric DLBCL.
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 石川県
  • Year and Date: 2015-10-16