Amino acid transporter in malignant lymphoma; its analysis and clinical application

• Project/Area Number: 16K10342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Radiation science
• Research Institution: Gunma University
• Principal Investigator: Tsukamoto Norifumi 群馬大学, 医学部附属病院, 准教授 (10292583)
• Co-Investigator(Kenkyū-buntansha): 横濱 章彦 群馬大学, 医学部附属病院, 准教授 (40323365) ; 三井 健揮 群馬大学, 医学部附属病院, 助教 (80420181) ; 滝沢 牧子 群馬大学, 大学院医学系研究科, 助教 (70613090)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 悪性リンパ腫 / アミノ酸トランスポーター / アミノ酸代謝 / FAMT-PET / MIB1 / FAMT / 免疫組織化学 / リアルタイムPCR / 免疫組織化学染色

Outline of Final Research Achievements

Expression of amino acid transporter and its related protein LAT1, ASCT2 and CD98 on lymphoma cells using real-time PCR was analyzed and reveal that these expressions were enhanced in half or lymphoma cell lines. Based on these data, immunohistological staining of LAT-1 and MIB1 were performed in 112 of lymphoma patients. In diffuse large cell lymphoma patients, almost of all cases were strongly positive, while this expression was low (5-30%) in indolent lymphoma such as follicular lymphoma, marginal-zone B-cell lymphoma and small lymphocytic lymphoma. The relation to MIB1 and CD98 are now analyzing.
FAMT-PET was performed in 11 of follicular lymphoma patient.

Academic Significance and Societal Importance of the Research Achievements

アミノ酸トランスポーターおよび関連する蛋白LAT1、ASCT-2、CD98は、リンパ腫細胞株で発現が亢進していた。リンパ腫症例の臨床検体でのアミノ酸トランスポーターLAT-1の発現の強さは、Aggressiveタイプ＞Indolentタイプであり、LAT-1関連分子であるCD98も同様の傾向であった。
増殖能の高いタイプでアミノ酸トランスポーターが発現していることは、その阻害により細胞増殖を抑えられる可能性があり、リンパ腫治療の新たな戦略となりうる。

Research Products

• [Journal Article] Prognostic impact of trisomy 21 in follicular lymphoma. (2019)
  • Author(s): Mitsui T, Yokohama A, Koiso H, Saito A, Toyama K, Shimizu H, Ishizaki T, Irisawa H, Takizawa M, Saitoh T, Murayama K, Matsumoto M, Handa H, Hirato J, Kojima M, Murakami H, Tsukamoto N.
  • Journal Title: Br J Haematol. Volume: 184 Issue: 4 Pages: 570-577
  • DOI: 10.1111/bjh.15664
  • Peer Reviewed / Open Access
• [Journal Article] Tumor long-axis diameter and SUVmax predict long-term responders in 90Y-ibritumomab tiuxetan monotherapy. (2019)
  • Author(s): Tsukamoto N, Yokohama A, Higuchi T, Mitsui T, Koiso H, Takizawa M, Shimizu H, Ishizaki T, Matsumoto M, Toyama K, Sakura T, Ogura H, Saitoh T, Ishida F, Murakami H, Tsushima Y, Handa H.
  • Journal Title: Int J Hematol. Volume: 109 Issue: 1 Pages: 91-97
  • DOI: 10.1007/s12185-018-2526-z
  • Peer Reviewed / Open Access
• [Journal Article] Human telomerase reverse transcriptase expression in a CD34-positive hematopoietic progenitor of myelodysplastic syndrome and acute myelogenous leukemia. (2019)
  • Author(s): Handa H, Nishimoto N, Inoue M, Yokohama A, Tsukamoto N, Saitoh T, Murakami H.
  • Journal Title: Hematol Oncol. Volume: - Issue: 4 Pages: 520-522
  • DOI: 10.1002/hon.2620
  • Peer Reviewed
• [Journal Article] Association between OGG1 S326C CC genotype and elevated relapse risk in acute myeloid leukemia. (2018)
  • Author(s): Gotoh N, Saitoh T, Takahashi N, Kasamatsu T, Minato Y, Lobna A, Oda T, Hoshino T, Sakura T, Shimizu H, Takizawa M, Handa H, Yokohama A, Tsukamoto N, Murakami H.
  • Journal Title: Int J Hematol Volume: 108 Issue: 3 Pages: 246-253
  • DOI: 10.1007/s12185-018-2464-9
  • Peer Reviewed
• [Journal Article] Early disease progression in patients with localized NK/T-cell lymphoma treated with concurrent chemoradiotherapy. (2018)
  • Author(s): Yamaguchi M, Suzuki R, Kim SJ, Ko YH, Oguchi M, Asano N, Miyazaki K, Terui Y, Kubota N, Maeda T, Kobayashi Y, Amaki J, Soejima T, Saito B, Shimoda E, Fukuhara N, Tsukamoto N, Shimada K, Choi I, Utsumi T, Ejima Y, Kim WS, Katayama N.
  • Journal Title: Cancer Sci Volume: - Issue: 6 Pages: 2056-2062
  • DOI: 10.1111/cas.13597
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Short-term administration of recombinant human erythropoietin decreases B cell number in human peripheral blood. (2018)
  • Author(s): Nagashima T, Yokohama A, Nagai K, Kasamatsu T, Gotoh N, Iriuchishima H, Sekigami T, Saitoh T, Handa H, Tsukamoto N, Murakami H.
  • Journal Title: Transfus Apher Sci. Volume: 57 Issue: 2 Pages: 208-214
  • DOI: 10.1016/j.transci.2018.01.009
  • Peer Reviewed
• [Journal Article] Clinical management and outcomes of completely resected stage I follicular lymphoma (2018)
  • Author(s): Yokohama A, Hashimoto Y, Takizawa M, Shimizu H, Miyazawa Y, Saitoh A, Toyama K, Ishizaki T, Mitsui T; Hiromi; Koiso, Saitoh T, Murayama K, Matsumoto M, Sawamura M, Murakami H, Hirato J, Kojima M, Nojima Y, Handa H, Tsukamoto N.
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 58 Issue: 1 Pages: 10-16
  • DOI: 10.3960/jslrt.17031
  • NAID: 130006512993
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed / Open Access
• [Journal Article] A Rare Case of Chronic Active Epstein-Barr Virus (EBV) Infection Accompanied by the Infiltration of EBV-infected CD8+ T Cells into the Muscle. (2017)
  • Author(s): Kobayashi N, Mitsui T, Ogawa Y, Iriuchishima H, Takizawa M, Yokohama A, Saitoh T, Koiso H, Tsukamoto N, Murakami H, Nojima Y, Handa H
  • Journal Title: J Pediatr Hematol Oncol. Volume: 36 Issue: 3 Pages: 196-201
  • DOI: 10.1097/mph.0000000000001026
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent alterations of the WW domain containing oxidoreductase gene spanning the common fragile site FRA16D in multiple myeloma and monoclonal gammopathy of undetermined significance. (2017)
  • Author(s): Handa H, Sasaki Y, Hattori H, Alkebsi L, Kasamatsu T, Saitoh T, Mitsui T, Yokohama A, Tsukamoto N, Matsumoto M, Murakami H.
  • Journal Title: Oncol Lett. Volume: 14 Issue: 4 Pages: 4372-4378
  • DOI: 10.3892/ol.2017.6672
  • Peer Reviewed / Open Access
• [Journal Article] Long non-coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma. (2017)
  • Author(s): Handa H, Kuroda Y, Kimura K, Masuda Y, Hattori H, Alkebsi L, Matsumoto M, Kasamatsu T, Kobayashi N, Tahara KI, Takizawa M, Koiso H, Ishizaki T, Shimizu H, Yokohama A, Tsukamoto N, Saito T, Murakami H.
  • Journal Title: Br J Haematol Volume: 179 Issue: 3 Pages: 449-460
  • DOI: 10.1111/bjh.14882
  • Peer Reviewed / Open Access
• [Journal Article] Retrospective analysis of prognostic factors for Waldenstroem macroglobulinemia: a multicenter cooperative study in Japan. (2017)
  • Author(s): Saito A, Isoda A, Kojima M, Yokohama A, Tsukune Y, Sasaki M, Ito S, Ohtsu A, Koike M, Murayama K, Moriya K, Tamura H, Matsumoto M, Nakahashi H, Tanosaki S, Sakura T, Kawamura T, Miyanaga T, Nakamura N, Murakami H, Handa H, Tsukamoto N
  • Journal Title: Int J Hematol. Volume: 106 Issue: 5 Pages: 681-690
  • DOI: 10.1007/s12185-017-2297-y
  • Peer Reviewed / Open Access
• [Journal Article] Overexpression of B-cell lymphoma 6 alters gene expression profile in a myeloma cell line and is associated with decreased DNA damage response. (2017)
  • Author(s): Tahara K, Takizawa M, Yamane A, Osaki Y, Ishizaki T, Mitsui T, Yokohama A, Saitoh T, Tsukamoto N, Matsumoto M, Murakami H, Nojima Y, Handa H.
  • Journal Title: Cancer Sci Volume: 108 Issue: 8 Pages: 1556-1564
  • DOI: 10.1111/cas.13283
  • Peer Reviewed / Open Access
• [Journal Article] Chromosome 16q genes CDH1, CDH13 and ADAMTS18 are correlated and frequently methylated in human lymphoma. (2016)
  • Author(s): Alkebsi L, Handa H, Yokohama A, Saitoh T, Tsukamoto N, Murakami H.
  • Journal Title: Oncol Lett. Volume: 12 Pages: 3523-3530
  • Peer Reviewed / Open Access
• [Journal Article] Immunostimulation during and after R-CHOP therapy for B-cell lymphoma. (2016)
  • Author(s): Nagai K, Kasamatsu T, Ohmiya C, Nagashima T, Koiso H, Yokohama A, Handa H, Tsukamoto N, Gotoh N, Alkebsi L, Saito T, Hayashi K, Murakami H.
  • Journal Title: Int J Exp Immunol Volume: 1 Pages: 1-7
  • Peer Reviewed
• [Presentation] Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinases Is Associated with Multiple Myeloma Progression, Prognosis and Extramedullary Plasmacytoma (2018)
  • Author(s): Rei Ishihara, Yuki Murakami, Kazuki Homma, Saki Watanabe, Tsukasa Oda, Masanobu Sunaga, Eiko Yamane, Nobuhiko Kobayashi, Yohei Osaki, Takuma Ishizaki, Hiroaki Shimizu, Hirono Iriuchishima, Hiromi Koiso, Norifumi Tsukamoto, Akihiko Yokohama, Gotoh Nanami, Rumi Ino, Takayuki Saitoh, Hirokazu Murakami, Hiroshi Handa
  • Organizer: 米国血液学会
• [Presentation] CD5陽性DLBCLに対する自家移植の検討 (2018)
  • Author(s): 松村 郁子, 清水 啓明, 飯野 宏允, 内藤 千晶, 宮澤 悠里, 石埼 卓馬, 外山 耕太郎, 小磯 博美, 横濱 章彦, 松本 守生, 小倉 秀充, 塚本 憲史, 平戸 純子, 半田 寛
  • Organizer: 日本血液学会
• [Presentation] リンパ球増多生を契機に診断されたマントル細胞リンパ腫と濾胞性リンパ腫のComposite lymphomaの一例. (2018)
  • Author(s): 石埼卓馬、横濱章彦、松本久美子、入内島裕乃、清水啓明、小磯博美、平戸純子、唐澤正光、塚本憲史、半田寛
  • Organizer: 日本リンパ網内系学会
• [Presentation] CD5陽性DLBCLに対する自家移植の検討 (2018)
  • Author(s): 松村郁子、清水啓明、内藤千晶、宮沢悠里、石埼卓馬、外山耕太郎、小磯博美、横濱章彦、松本守生、小倉秀充、塚本憲史、半田寛
  • Organizer: 造血幹細胞移植学会
• [Presentation] Efficacy of 80% R-CHOP for patients with diffuse large B cell lymphoma aged 71 years and older. (2017)
  • Author(s): Shuhei Kanaya, Takeki Mitsui, Akihiko Yokohama, Norifumi Tsukamoto et al
  • Organizer: 日本血液学会
• [Presentation] Early progression of disease in patients with newly diagnosed localized ENKL treated with RT-DeVIC (2017)
  • Author(s): Ritsuro Suzuki, Motoko Yamaguchi, Norifumi Tsukamoto et al
  • Organizer: 日本血液学会
• [Presentation] Cytogenetic Alterations Are Differently Associated with Disease Progression Depending on t(14;18) in Follicular Lymphoma (2017)
  • Author(s): Akihiko Yokohama, Takeki Mitsui, Hiromi Koiso, Norifumi Tsukamoto et al
  • Organizer: 米国血液学会
• [Presentation] Clinical feature and MYD88 mutation in 12 case of LPL with non-IgM paraproteinemia. (2017)
  • Author(s): Hiromi Koiso、Akihiko Yokohama, Takemi Mitsui, Norifumi Tsukamoto et al
  • Organizer: 日本血液学会