Identification of myeloma stem cells and its clinical application

• Project/Area Number: 22591047
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Jichi Medical University
• Principal Investigator: FURUKAWA Yusuke 自治医科大学, 医学部, 教授 (00199431)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 癌 / 遺伝子 / 発現制御 / 移植再生医療 / 移植・再生医療

Research Abstract

Although myeloma tissues look homogenous,it has been demonstrated from the 70s that cells with clonogenic growth potential exist only 1 in 100 to 100,000 myeloma cells. Recent investigations indicate that myeloma stem cells express CD19 and CD27 but not C

Research Products

• [Journal Article] Homopiperazine Derivatives as a Novel Class of Proteasome Inhibitors with a Unique Mode of Proteasome Binding (2013)
  • Author(s): Kikuchi, J., Shibayama, N., Yamada, S., Wada, T., Nobuyoshi, M., Izumi, T., Akutsu, M., Kano, Y., Sugiyama, K., Ohki, M., Park, S.-Y. and Furukawa, Y.
  • Journal Title: PLoS One Volume: 8
• [Journal Article] BCR-ABL Regulates Death Receptor Expression for TNF-related Apoptosis-inducing Ligand (TRAIL) in Philadelphia Chromosome-positive Leukemia. (2013)
  • Author(s): Kuroda, I., Inukai, T., Zhang, X., Kikuchi, J., Furukawa, Y., Nemoto, A., Akahane, K., Hirose, K., Honna-Ooshiro, H., Goi, K., Kagami, K., Yagita, H., Tauchi, T., Maeda, Y. and Sugita, K.
  • Journal Title: Oncogene Volume: 32 Pages: 1670-1681
• [Journal Article] Homopiperazine Derivatives as a Novel Class of Proteasome Inhibitors with a Unique Mode of Proteasome Binding. (2013)
  • Author(s): Kikuchi J.
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e60649-e60649
  • DOI: 10.1371/journal.pone.0060649
  • Peer Reviewed
• [Journal Article] Histone Deacetylase 1 Enhances microRNA Processing via Deacetylation of DGCR8 (2012)
  • Author(s): Wada, T., Kikuchi, J. and Furukawa, Y.
  • Journal Title: EMBO Rep Volume: 13 Pages: 142-149
• [Journal Article] Latexin Regulates the Abundance of Multiple Cellular Proteins in Hematopoietic Stem Cells. (2012)
  • Author(s): Mitsunaga, K., Kikuchi, J., Wada, T. and Furukawa, Y.
  • Journal Title: J. Cell. Physiol Volume: 227 Pages: 1138-1147
• [Journal Article] Promoter Methylation Confers Kidney-specific Expression of the Klotho Gene. (2012)
  • Author(s): Azuma, M., Koyama, D., Kikuchi, J., Yoshizawa, H., Thasinas, D., Shiizaki, K., Kuro-o, M., Furukawa, Y. and Kusano, E.
  • Journal Title: FASEB J Volume: 26 Pages: 4264-4274
• [Journal Article] Reduced Histone H3K9 Acetylation of Clock Genes and Abnormal Glucose Metabolism in ob/ob Mice (2012)
  • Author(s): Ishikawa-Kobayashi, E., Ushijima, K., Ando, H., Maekawa, T., Takuma, M., Furukawa, Y. and Fujimura, A.
  • Journal Title: Chronobiol. Int Volume: 29 Pages: 982-993
• [Journal Article] Promoter Methylation Confers Kidney-specific Expression of the Klotho Gene. (2012)
  • Author(s): Azuma M.
  • Journal Title: FASEB Journal Volume: 26 Issue: 10 Pages: 4264-4274
  • DOI: 10.1096/fj.12-211631
  • Peer Reviewed
• [Journal Article] Reduced Histone H3K9 Acetylation of Clock Genes and Abnormal GlucoseMetabolism in ob/ob Mice. (2012)
  • Author(s): Ishikawa-Kobayashi E.
  • Journal Title: Chronobiology International Volume: 29 Issue: 8 Pages: 982-993
  • DOI: 10.3109/07420528.2012.706765
  • Peer Reviewed
• [Journal Article] Histone deacetylase 1 enhances microRNA processing via deacetylation of DGCR8 (2012)
  • Author(s): Wada T, Kikuchi J, Furukawa Y
  • Journal Title: EMBO Reports Volume: 13 Issue: 2 Pages: 142-149
  • DOI: 10.1038/embor.2011.247
  • Peer Reviewed
• [Journal Article] Latexin regulates the abundance of multiple cellular proteins in hematopoietic stem cells (2012)
  • Author(s): Mitsunaga K, Kikuchi J, Wada T, Furukawa Y
  • Journal Title: Journal of Cellular Physiology Volume: 227 Issue: 3 Pages: 1138-1147
  • DOI: 10.1002/jcp.22834
  • Peer Reviewed
• [Journal Article] Seven-year Follow-up of Patients Receiving Imatinib for the Treatment of Newly Diagnosed Chronic Myelogenous Leukemia by the TARGET System (2011)
  • Author(s): Tauchi, T., Kizaki, M., Okamoto, S., Tanaka, H., Tanimoto, M., Inokuchi, K., Murayama, T., Saburi, Y., Hino, M., Tsudo, M., Shimomura, T., Isobe, Y., Oshimi, K., Dan, K., Ohyashiki, K, Ikeda, Y. and the TARGET Investigators (including Furukawa, Y.)
  • Journal Title: Leuk. Res Volume: 35 Pages: 585-590
• [Journal Article] Histone Deacetylases Are Critical Targets of Bortezomib-induced Cytotoxicity in Multiple Myeloma (2010)
  • Author(s): Kikuchi, J., Wada, T., Shimizu, R., Izumi, T., Akutsu, M., Mitsunaga, K., Noborio-Hatano, K., Nobuyoshi, M., Ozawa, K., Kano, Y. and Furukawa, Y.
  • Journal Title: Blood Volume: 116 Pages: 406-417
• [Journal Article] HDAC Inhibitors Augment Cytotoxic Activity of Rituximab by Upregulating CD20 Expression on Lymphoma Cells (2010)
  • Author(s): Shimizu, R., Kikuchi, J., Wada, T., Ozawa, K., Kano, Y. and Furukawa, Y.
  • Journal Title: Leukemia Volume: 24 Pages: 1760-1768
• [Journal Article] MSK1 Activation in Acute Myeloid Leukemia Cells with FLT3 Mutations (2010)
  • Author(s): Odgerel, T., Kikuchi, J., Wada, T., Shimizu, R., Kano, Y. and Furukawa, Y.
  • Journal Title: Leukemia Volume: 24 Pages: 1087-1090
• [Journal Article] Aberrant Induction of LMO2 by the E2A-HLF Chimeric Transcription Factor and Its Implication in Leukemogenesis of B-Precursor ALL with t(17;19) (2010)
  • Author(s): Hirose, K., Inukai,T., Kikuchi, J., Furukawa, Y., Ikawa, T., Kawamoto, H., Oram, S.H., Gottgens, B., Kiyokawa, N., Miyagawa, Y., Okita, H., Akahane, K., Zhang, X., Kuroda, I., Honna, H., Kagami, K., Goi, K., Kurosawa, H., Look, A.T., Matsui, H., Inaba, T.
  • Journal Title: Blood Volume: 116 Pages: 962-970
• [Journal Article] Up-regulation of Survivin by the E2A-HLF Chimera Is Indispensable for the Survival of t(17;19)-positive Leukemia Cells (2010)
  • Author(s): Okuya, M., Kurosawa, H., Kikuchi, J., Furukawa, Y., Matsui, H., Aki, D., Matsunaga, T., Inukai, T., Goto, H., Altura, R.A., Sugita, K., Arisaka, O., Look, A.T. and Inaba, T.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 1850-1860
• [Journal Article] Vinculin Is Indispensable for Repopulation by Hematopoietic Stem Cells, Independent of Integrin Function. (2010)
  • Author(s): Ohmori, T., Kashiwakura, Y., Ishiwata, A., Madoiwa, S., Mimuro, J., Furukawa, Y. and Sakata, Y.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 31763-31773
• [Journal Article] Inactivation of the Retinoblastoma Protein by Mutant B-Raf in Malignant Melanoma (2010)
  • Author(s): Kobayashi, Y., Kobayashi, T., Kikuchi, J., Futaki, K., Wada, T., Kusano, E., Murata, S., Ohtsuki, M. and Furukawa, Y.
  • Journal Title: Nature Precedings
• [Journal Article] Histone deacetylases are critical targets of bortezomib-induced… (2010)
  • Author(s): Kikuchi, J.Wada, T., et al.
  • Journal Title: Blood Volume: 116 Pages: 406-417
  • Peer Reviewed
• [Journal Article] HDAC inhibitors augment cytotoxic activity of rituximab… (2010)
  • Author(s): Shimizu, R., Kikuchi, J., et al.
  • Journal Title: Leukemia Volume: 24 Pages: 1760-1768
  • Peer Reviewed
• [Journal Article] MSK1 activation in acute myeloid leukemia cells with FLT3 mutations. (2010)
  • Author(s): Odgerel, T., Kikuchi, J., et al.
  • Journal Title: Leukemia Volume: 24 Pages: 1087-1092
  • Peer Reviewed
• [Journal Article] The Novel Orally Active Proteasome Inhibitor K-7174 Exerts Anti-myeloma Activity in vitro and in vivo by Down-regulating the Expression of Class I Histone Deacetylases.
  • Author(s): Kikuchi, J., Yamada, S., Koyama, D., Wada, T., Nobuyoshi, M., Izumi, T., Akutsu, M., Kano, Y. and Furukawa, Y.
  • Journal Title: J. Biol. Chem Volume: (in press)
• [Presentation] Bortezomib Overcomes the Cell Adhesion-mediated Drug Resistance by Down-regulating HDAC Expression in Multiple Myeloma. (2013)
  • Author(s): Furukawa, Y. and Kikuchi, J.
  • Organizer: The 14th Intenational Myeloma Workshop
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2013-04-04
• [Presentation] How to overcome the cell adhesion-mediated drug resistance in multiple myeloma (2012)
  • Author(s): 古川雄祐
  • Organizer: 第74回日本血液学会学術総会、Symposium 6 "Multiple Myeloma: Topics in Basic Science Applicable to the Development of Novel Therapies"
  • Place of Presentation: 京都
  • Year and Date: 2012-10-21
• [Presentation] Multiple Myeloma Cells Acquire Anti-cancer Drug Resistnce via Interaction with Bone Marrow Microenvironment (2012)
  • Author(s): Furukawa, Y.
  • Organizer: The 9th Nikko Intenational Symposium
  • Place of Presentation: Shimotuke, Tochigi, Japan
  • Year and Date: 2012-10-12
• [Presentation] Low HDAC expression contributes to insufficient maturation of microRNAs in hematopoietic stem cells (2011)
  • Author(s): 和田妙子、菊池次郎、古川雄祐
  • 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] Latexin regulates the abundance of multiple cellular proteins in hematopoietic stem cells (2011)
  • Author(s): 光永佳奈枝、菊池次郎、和田妙子、古川雄祐
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-14
• [Presentation] Latexin Regulates the Abundance of Multiple Cellular Proteins in Hematopoietic Stem Cells. (2011)
  • Author(s): Mitsunaga, K., Kikuchi, J., Wada, T. and Furukawa, Y.
  • Organizer: The XXV Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Place of Presentation: Hongo, Tokyo
  • Year and Date: 2011-09-15
• [Presentation] Multiple myeloma: Introduction of novel drugs with unique mechanisms of action to overcome drug resistance (2011)
  • Author(s): 古川雄祐
  • Organizer: 第9回日本臨床腫瘍学会学術総会、日本臨床腫瘍学会/日本血液学会合同シンポジウム"分子標的治療薬導入から10年を迎えて"
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-21
• [Presentation] Multiple myeloma : Introduction of novel drugs with unique mechanisms of action to overcome drug resistance (2011)
  • Author(s): 古川雄祐
  • Organizer: 第9回日本臨床腫瘍学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-07-21
• [Presentation] Latexin Regulates the Abundance of Multiple Cellular Proteins in Hematopoietic Stem Cells. (2011)
  • Author(s): Mitsunaga, K., Kikuchi, J., Wada, T. and Furukawa, Y.
  • Organizer: The 9th Stem Cell Research Symposium
  • Place of Presentation: Roppongi、Tokyo, Japan
  • Year and Date: 2011-05-14
• [Presentation] ボルテゾミブの抗骨髄腫作用はヒストン脱アセチル化酵素の発現抑制を介する (2010)
  • Author(s): 菊池次郎、和田妙子、清水瑠美、和泉透、光永佳奈枝、畑野かおる、信吉正治、小澤敬也、加納康彦、古川雄祐
  • Organizer: 第35回日本骨髄腫研究会総会
  • Place of Presentation: 富山
  • Year and Date: 2010-11-20
• [Presentation] ボルテゾミブによる接着耐性の解除と骨髄腫治療戦略への組み込み (2010)
  • Author(s): 古川雄祐
  • Organizer: 厚生労働省がん研究助成金木崎班班会議特別講演
  • Place of Presentation: 東京
  • Year and Date: 2010-01-23
• [Presentation] How to overcome the cell adhesion-mediated drug resistance in multiple myeloma.
  • Author(s): 古川雄祐
  • Organizer: 第74回日本血液学会学術総会
  • Place of Presentation: 京都
  • Invited
• [Book] Klotho遺伝子の発現調節機構。Annual Review 腎臓 (2012)
  • Author(s): 古川雄祐、東昌広、草野英二
  • Publisher: 中外医学社
• [Book] Klotho遺伝子の発現調節機構。腎と透析 72 (2012)
  • Author(s): 東昌広、古川雄祐、草野英二
  • Publisher: 中外医学社
• [Book] 多発性骨髄腫の薬剤耐性化とボルテゾミブの抗がん剤併用による抗腫瘍効果増強、血液フロンティア22 (2012)
  • Author(s): 菊池次郎、古川雄祐
• [Book] ボルテゾミブの新たな作用機序と他剤との併用の理論的妥当性。血液内科 64 (2012)
  • Author(s): 古川雄祐、菊池次郎
• [Book] 造血器腫瘍の治療標的としてのDNA 修復機構。血液内科 64 (2012)
  • Author(s): 小山大輔、古川雄祐
• [Book] ヒストン脱アセチル化酵素阻害剤による多発性骨髄腫の治療。医学のあゆみ 242 (2012)
  • Author(s): 菊池次郎、古川雄祐
• [Book] ボルテゾミブの新たな作用機序:エピジェネティック制御を介する骨髄腫細胞の制御。, 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): 菊池次郎、古川雄祐, 木崎昌弘編
  • Publisher: 医薬ジャーナル社
• [Book] アルキル化剤の作用機序、適応、副作用。血液内科 65 (2012)
  • Author(s): 平岡信弥、古川雄祐
• [Book] 骨髄腫細胞と間質細胞の相互作用:薬剤耐性とその対策。BIO Clinica27 (2012)
  • Author(s): 菊池次郎、古川雄祐
• [Book] B白血病/リンパ芽球性リンパ腫。押味和夫編、悪性リンパ腫の基礎と臨床 改訂版 (2011)
  • Author(s): 古川雄祐、加納康彦
  • Publisher: 医薬ジャーナル社
• [Book] 新規抗腫瘍薬ベンダムスチンの作用機序と臨床効果。日薬理誌(新規抗腫瘍薬ベンダムスチンの作用機序と臨床効果。日薬理誌(Folia Pharmacol. Jpn) 1382 (2011)
  • Author(s): 古川雄祐、平岡信弥、和田妙子、菊池次郎、加納康彦
• [Book] 多発性骨髄腫における細胞死の抑制。血液内科62 (2011)
  • Author(s): 古川雄祐、菊池次郎
• [Book] 骨髄腫幹細胞を標的とする薬剤。最新医学66 (2011)
  • Author(s): 古川雄祐、菊池次郎
• [Book] ヒストン脱アセチル化酵素阻害剤によるリツキシマブ耐性の克服。血液内科62 (2011)
  • Author(s): 古川雄祐、清水瑠美、和田妙子、菊池次郎
• [Book] 血漿蛋白とその働き。 図説臨床看護医学(エディターシップ) 5: [1. 1] (2011)
  • Author(s): 古川雄祐、小澤敬也監修
  • Total Pages: 3
• [Book] 血清蛋白の検査, 小澤敬也監修、図説臨床看護医学(エディターシップ) 5:[3] (2011)
  • Author(s): 古川雄祐, 小澤敬也監修
  • Total Pages: 7
• [Book] 染色体分析とFISH,図説臨床看護医学(エディターシップ) 5:[3] (2011)
  • Author(s): 古川雄祐, 小澤敬也監修
  • Total Pages: 10
• [Book] 白血球減少症と無顆粒球症, 図説臨床看護医学(エディターシップ) 5:[4.2] (2011)
  • Author(s): 古川雄祐, 小澤敬也監修
  • Total Pages: 1
• [Book] 好中球機能異常症, 図説臨床看護医学(エディターシップ) 5:[4.2] (2011)
  • Author(s): 古川雄祐, 小澤敬也監修
  • Total Pages: 15
• [Book] ボルテゾミブによる未治療多発性骨髄腫の治療戦略。血液フロンティア 21 (2011)
  • Author(s): 木崎昌弘、Meletios A.Demopoulos、安部正博、石田禎夫、古川雄祐
• [Book] 多発性骨髄腫における薬剤耐性機序。Annual Review血液 (2010)
  • Author(s): 古川雄祐、菊池次郎
  • Publisher: 中外医学社
• [Book] 骨髄腫幹細胞研究の進展。血液・腫瘍科、61 (2010)
  • Author(s): 菊池次郎、古川雄祐
• [Remarks]
  • URL: http://www.jichi.ac.jp/stem/index.html
• [Remarks]
  • URL: http://www.jichi.ac.jp/stem/index.html
• [Remarks]
  • URL: http://www.jichi.ac.jp/stem/index.html
• [Patent(Industrial Property Rights)] ホモピペラジン化合物を主成分とするプロテアソーム阻害剤
  • Inventor(s): 菊池次郎・古川雄祐
  • Industrial Property Rights Holder: 菊池次郎・古川雄祐
  • Industrial Property Number: 2011-013923