The role of Mastermind in B-cell lymphoma

• Project/Area Number: 23590413
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Saitama Medical University
• Principal Investigator: HIGASHI Morihiro 埼玉医科大学, 医学部, 講師 (00323395)
• Co-Investigator(Kenkyū-buntansha): TAMARU Jun-ichi 埼玉医科大学, 医学部, 教授 (30188429)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血液 / B細胞性リンパ腫 / Mastermind / Notch / 悪性リンパ腫 / 腫瘍発生機構 / LR11 / Notchシグナル / 免疫組織化学 / Matermind

Research Abstract

Mastermind (Mam) is a pivotal modulator of Notch signaling and has essential roles in the differentiation of B-cells from GC to MZ. We showed that 1) MamL1 and MamL3 were expressed in the GC and MZ of reactive lymph node. 2) Mam was expressed in 50% of cases with MC subtype of the Hodgkin lymphoma, whereas the expression was low in the cases with NS subtype. 3) Mam was expressed in the cases with follicular lymphoma and was low in the cases with marginal zone lymphoma. 4) The expression of Hes-1 was correlated with the expression of Notch1 or Jag2 in lymphoma cell lines, suggesting the Notch pathway is activated by cell-autonomously within lymphoma cell lines. 5) The expression of Hes-1 was correlated with LR11 expression. LR11 may be activated in parallel with Notch activation. Further investigation of the expression of Notch related molecules and the status of Notch activation is needed to clarify the biological and pathological differences in B-cell lymphomas originated from the GC.

Research Products

• [Journal Article] Potential utility of serum soluble LR11 as a diagnostic biomarker for intravascular large B-cell lymphoma (2014)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Higashi M, Fujikawa K, Matsue K, Yokote K, Tamaru JI, Bujo H, Nakaseko C
  • Journal Title: Leuk Lymphoma Volume: (印刷中) Issue: 10 Pages: 2391-2394
  • DOI: 10.3109/10428194.2014.880430
  • Peer Reviewed / Open Access
• [Journal Article] G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow (2014)
  • Author(s): Shimizu N, Nakaseko C, Jiang M, Nishii K, Yokote K, Iseki T, Higashi M, Tamaru J, Schneider WJ, Bujo H
  • Journal Title: Ann Hematol Volume: (印刷中) Issue: 7 Pages: 1111-1122
  • DOI: 10.1007/s00277-014-2033-0
  • Peer Reviewed / Open Access
• [Journal Article] G-CSF induces the release of the soluble form of LR11, a regulator of myeloid cell mobilization in bone marrow. (2014)
  • Author(s): Shimizu N, Nakaseko C, Jiang M, Nishii K, Yokote K, Iseki T, Higashi M, Tamaru J, Schneider WJ, Bujo H.
  • Journal Title: Ann Hematol. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Potential utility of serum soluble LR11 as a diagnostic biomarker for intravascular large B-cell lymphoma. (2014)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Higashi M, Fujikawa K, Matsue K, Yokote K, Tamaru JI, Bujo H, Nakaseko C.
  • Journal Title: Leuk Lymphoma. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] LR11 : a novel biomarker identified in follicular lymphoma (2013)
  • Author(s): Kawaguchi T, Ohwada C, Takeuchi M, Shimizu N, Sakaida E, Takeda Y, Sakai S, Tsukamoto S, Yamazaki A, Sugita Y, Jiang M, Higashi M, Yokote K, Tamura J, Bujo H, Nakaseko C
  • Journal Title: Br J Haematol Volume: 163(2) Issue: 2 Pages: 277-280
  • DOI: 10.1111/bjh.12467
  • Peer Reviewed
• [Journal Article] Expression of Epstein-Barr Virus-Encoded Proteins in Extranodal NK/T-cell Lymphoma, Nasal Type (ENKL): Differences in Biologic and Clinical Behaviors of LMP1-Positive and -Negative ENKL (2012)
  • Author(s): Kanemitsu N, Isobe Y, Masuda A, Momose S, Higashi M, Tamaru J, Sugimoto K, Komatsu N
  • Journal Title: Clin Cancer Res. Volume: 18(8) Pages: 2164-72
  • Peer Reviewed
• [Journal Article] Tumor promoting effect of podoplanin-positive fibroblasts is mediated by enhanced RhoA activity. (2012)
  • Author(s): Ito S, Ishii G, Hoshino A, Hashimoto H, Neri S, Kuwata T, Higashi M, Nagai K, Ochiai A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 442 Issue: 1 Pages: 194-9
  • DOI: 10.1016/j.bbrc.2012.04.158
  • Peer Reviewed
• [Journal Article] Expression of Epstein-Barr Virus-Encoded Proteins in Extranodal NK/T-cell Lymphoma, Nasal Type (ENKL): Differences in Biologic and Clinical Behaviors of LMP1-Positive and -Negative ENKL. (2012)
  • Author(s): Kanemitsu N,
  • Journal Title: Clin Cancer Res. Volume: 18（8） Issue: 8 Pages: 2164-2172
  • DOI: 10.1158/1078-0432.ccr-11-2395
  • Peer Reviewed
• [Journal Article] Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas (2011)
  • Author(s): Yamaguchi H, Kuboki Y, Hatori T, Yamamoto M, Shiratori K, Kawamura S, Kobayashi M, Shimizu M, Ban S, Koyama I, Higashi M, et. al
  • Journal Title: Am J Surg Pathol Volume: 35(12) Pages: 1812-7
  • Peer Reviewed
• [Journal Article] 【分子病態からみた血液疾患診療の進歩】ホジキンリンパ腫の病態解析の新展開 (2011)
  • Author(s): 東守洋,田丸淳一
  • Journal Title: 血液内科 Volume: 62巻4号 Pages: 448-454
• [Journal Article] Somatic mutations in PIK3CA and activation of AKT in intraductal tubulopapillary neoplasms of the pancreas (2011)
  • Author(s): Yamaguchi H, Kuboki Y, Hatori T, Yamamoto M, Shiratori K, Kawamura S, Kobayashi M, Shimizu M, Ban S, Koyama I, Higashi M, et. al.
  • Journal Title: Am J Surg Pathol. Volume: 35(12) Pages: 1812-7
  • Peer Reviewed
• [Journal Article] 【分子病態からみた血液疾患診療の進歩】 ホジキンリンパ腫の病態解析の新展開 (2011)
  • Author(s): 東 守洋, 田丸淳一
  • Journal Title: 血液内科 Volume: 62巻4号 Pages: 448-454
• [Presentation] LR11: implications for molecular targeting therapy in lymphoma (2013)
  • Author(s): Morihiro Higashi, Michihide Tokuhira, Takeharu Kawaguchi, Masahiro Takeuchi, Chikako Ohwada, Chiaki Nakaseko, Toshiki Watanabe, Hideaki Bujo, Masahiro Kizaki, Jun-ichi Tmaru
  • Organizer: 2nd Joint Scientific Meeting Medical University of Vienna and Chiba University
  • Place of Presentation: ウィーン,オーストリア
  • Year and Date: 2013-02-15
• [Presentation] 悪性リンパ腫におけるLR11発現と意義 (2012)
  • Author(s): 東守洋, 得平道英, 川口岳晴, 竹内正博, 大和田千佳子, 中世古知明, 武成英明, 木崎昌弘, 田丸淳一
  • Organizer: 悪性リンパ腫治療研究会
  • Place of Presentation: 京都
  • Year and Date: 2012-03-03
• [Presentation] Expression of LR11 in malignant lymphoma (2011)
  • Author(s): 東守洋, 得平道英, 川口岳晴, 竹内正博, 大和田千佳子, 中世古知明, 武成英明, 木崎昌弘, 田丸淳一
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-15
• [Presentation] LR11 repressed Rituximab Cytotoxity in B-cell lymphoma.
  • Author(s): 東 守洋、得平道英、川口岳晴、武内正博、大和田千佳子、中世古知明、武城英明、木崎昌弘、田丸淳一
  • Organizer: 第75回日本血液学会総会
  • Place of Presentation: 札幌
• [Presentation] 悪性リンパ腫におけるLR11発現とその意義
  • Author(s): 東守洋, 得平道英, 川口岳晴, 武内正博, 大和田千佳子, 中世古知昭, 渡邊俊樹, 武城英明, 木崎昌弘, 田丸淳一
  • Organizer: 第101回日本病理学会総会
  • Place of Presentation: 東京、新宿、京王プラザホテル
• [Presentation] LR11 Expression in Malignant Lymphoma
  • Author(s): Morihiro Higashi, Michihide Tokuhira, Takeharu Kawaguchi, Masahiro Takeuchi, Chikako Ohwada, Chiaki Nakaseko, Toshiki Watanabe, Hideaki Bujo, Masahiro Kizaki, Jun-ichi Tmaru.
  • Organizer: The 3rd JSH International Symposium 2012 in Kawagoe
  • Place of Presentation: Prince Hotel Kawagoe, Kawagoe, Saitama
• [Book] 造血器腫瘍とエピジェネティクス -治療への応用と新たな展開- (2012)
  • Author(s): 東 守洋、田丸淳一 (木崎昌弘 編)
  • Total Pages: 10
  • Publisher: 医薬ジャーナル社