The metabolome analysis of leukemic stem cell

• Project/Area Number: 23591379
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: OHNISI Kazunori 浜松医科大学, 医学部附属病院, 教授 (80252170)
• Co-Investigator(Kenkyū-buntansha): FUJIE Michio 浜松医科大学, 実験実習機器センター, 技術専門職員 (90397373) ; SHIBATA Kiyoshi 浜松医科大学, 実験実習機器センター, 技術専門職員 (80397372) ; NAKAMURA Satoki 浜松医科大学, 医学部, 特任研究員 (20377740)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 白血病 / メタボローム解析 / 代謝制御 / 白血病幹/前駆細胞 / 代謝酵素阻害剤 / 白血病幹細胞 / 嫌気性代謝 / 代謝阻害剤

Research Abstract

We investigated the metabolome analysis in leukemic stem/progenitor cells. We found that hexokinase (HK), Phosphofructokinase 1 and 2 (PFK1 and 2) and Pyruvate Kinase (PK) were activated in leukemic stem/progenitor cells. We identified the inhibitors (3-BP, 3PO and Alkinnin) of these kinases as target molecules in leukemic stem/progenitor cells. We showed that these inhibitors inhibited the proliferation of leukemic stem/progenitor cells. We will perform the development of cancer stem cell-specific drugs for leukemia therapy.

Research Products

• [Journal Article] Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines. (2014)
  • Author(s): Nishida Y, Mizutani N, Inoue M, Omori Y, Tamiya-Koizumi K, Takagi A, Kojima T, Suzuki M, Nozawa Y, Minami Y, Ohnishi K, Naoe T, Murate T.
  • Journal Title: Biochim Biophys Acta. Volume: 1839 Issue: 4 Pages: 265-274
  • DOI: 10.1016/j.bbagrm.2014.02.004
  • Peer Reviewed
• [Journal Article] Impact of genetic and non-genetic factors on clinical responses to prochlorperazine in oxycodone-treated cancer patients. (2014)
  • Author(s): Tashiro M, Naito T, Ohnishi K, Kagawa Y, Kawakami J.
  • Journal Title: Clin Chim Acta. Volume: 429 Pages: 175-180
  • DOI: 10.1016/j.cca.2013.12.011
  • Peer Reviewed
• [Journal Article] Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: a retrospective analysis of JALSG-APL97. (2013)
  • Author(s): Fujita H, Asou N, Iwanaga M, Hyo R, Nomura S, Kiyoi H, Okada M, Inaguma Y, Matsuda M, Yamauchi T, Ohtake S, Izumi T, Nakaseko C, Ishigatsubo Y, Shinagawa K, Takeshita A, Miyazaki Y, Ohnishi K, Miyawaki S, Naoe T; Japan Adult Leukemia Study Group.
  • Journal Title: Cancer Sci Volume: 104 Issue: 10 Pages: 1339-1345
  • DOI: 10.1111/cas.12230
  • Peer Reviewed
• [Journal Article] Cancer cachexia raises the plasma concentration of oxymorphone through the reduction of CYP3A but not CYP2D6 in oxycodone-treated patients. (2013)
  • Author(s): Naito T, Tashiro M, Ishida T, Ohnishi K, Kawakami J.
  • Journal Title: J Clin Pharmacol. Volume: 53 Issue: 8 Pages: 812-818
  • DOI: 10.1002/jcph.112
  • Peer Reviewed
• [Journal Article] The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts. (2013)
  • Author(s): Ohnishi K
  • Journal Title: Blood Volume: 121 Issue: 22 Pages: 4439-42
  • DOI: 10.1182/blood-2013-03-490003
  • Peer Reviewed
• [Journal Article] Recovery of Kidney Function by Rituximab-based Therapy in a Patient with Waldenström's Macroglobulinemia-related Nephropathy Presenting Cast Nephropathy and Interstitial Lymphocytic Infiltration (2012)
  • Author(s): Miwa M, Sakao Y, Ishigaki S, Ono M, Fujikura T, Yasuda H, Suzuki H, Kato A, Nagata Y, Shigeno K, Nakamura S, Ohnishi K, Fujigaki Y
  • Journal Title: Internal Medicine Volume: 51 Issue: 13 Pages: 1725-1730
  • DOI: 10.2169/internalmedicine.51.7207
  • NAID: 130002062195
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] What can be seen by 18F-FDG PET in atherosclerosis imaging? The effect of foam cell formation on 18F-FDG uptake to macrophages in vitro (2012)
  • Author(s): Ogawa M, Nakamura S, Saito Y, Kosugi M, Magata Y
  • Journal Title: J Nucl Med Volume: 53(1) Issue: 1 Pages: 55-58
  • DOI: 10.2967/jnumed.111.092866
  • Peer Reviewed
• [Journal Article] The CRKL gene encoding an adaptor protein is amplified, overexpressed, and a possible therapeutic target in gastric cancer (2012)
  • Author(s): Natsume H, Shinmura K, Tao H, Igarashi H, Suzuki M, Nagura K, Goto M, Yamada H, Maeda M, Konno H, Nakamura S, Sugimura H
  • Journal Title: J Transl Med Volume: 10 Issue: 1 Pages: 97-97
  • DOI: 10.1186/1479-5876-10-97
  • Peer Reviewed
• [Journal Article] Down-regulation of Thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression (2012)
  • Author(s): Nakamura S, Yokota D, Tan L, Nagata Y, Takemura T, Hirano I, Shigeno K, Shibata K, Fujisawa S, Ohnishi K
  • Journal Title: Int J Cancer Volume: 130(5) Issue: 5 Pages: 1046-1059
  • DOI: 10.1002/ijc.26065
  • Peer Reviewed
• [Journal Article] What can be seen by 18F-FDG PET in atherosclerosis imaging? The effect of foam cell formation on 18F-FDG uptake to macrophages in vitro. (2012)
  • Author(s): Ogawa M, Nakamura S, Saito Y, Kosugi M, Magata Y.
  • Journal Title: J Nucl Med. Volume: 53 Pages: 55-58
  • Peer Reviewed
• [Journal Article] Bcr-Abl-mediated Raf kinase inhibitor protein suppression promotes chronic myeloid leukemia progenitor cells proliferation (2011)
  • Author(s): Nakamura S, Yagyu T, Takemura T, Tan L, Nagata Y, Yokota D, Hirano I, Shibata K, Fujie M, Fujisawa S, Ohnishi K
  • Journal Title: Stem Cell Discovery Volume: 1(3) Issue: 03 Pages: 54-66
  • DOI: 10.4236/scd.2011.13006
  • ISSN: 2161-6760, 2161-6787
  • Peer Reviewed
• [Journal Article] Activation of the interferon pathway in peripheral blood of patients with Sjogren's syndrome (2011)
  • Author(s): Kimoto O, Sawada J, Shimoyama K, Suzuki D, Nakamura S, Hayashi H, Ogawa N
  • Journal Title: J Rheumatol Volume: 38(2) Issue: 2 Pages: 310-316
  • DOI: 10.3899/jrheum.100486
  • Peer Reviewed
• [Journal Article] Small GTPase RAB45-mediated p38 activation in apoptosis of chronic myeloid leukemia progenitor cells (2011)
  • Author(s): Nakamura S, Takemura T, Tan L, Nagata Y, Yokota D, Hirano I, Shigeno K, Shibata K, Fujie M, Fujisawa S, Ohnishi K.
  • Journal Title: Carcinogenesis Volume: 32(12) Issue: 12 Pages: 1758-1772
  • DOI: 10.1093/carcin/bgr205
  • Peer Reviewed
• [Journal Article] Transcriptional repression of Cdc25B by IER5 inhibits the proliferation of leukemic progenitor cells through NF-YB and p300 in acute myeloid leukemia (2011)
  • Author(s): Nakamura S, Ohnishi K, et al
  • Journal Title: PLoS One Volume: 6(11) Issue: 11 Pages: e28011-e28011
  • DOI: 10.1371/journal.pone.0028011
  • Peer Reviewed
• [Journal Article] JmjC-domain containing histone demethylase 1B-mediated P15(Ink4b) suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia (2011)
  • Author(s): Nakamura S, Ohnishi K, et al
  • Journal Title: Molecular Carcinogenesis Volume: (In press) Issue: 1 Pages: 57-69
  • DOI: 10.1002/mc.20878
  • Peer Reviewed
• [Journal Article] JmjC-domain containing histone demethylase 1B-mediated p15(Ink4b) suppression promotes the proliferation of leukemic progenitor cells through modulation of cell cycle progression in acute myeloid leukemia. (2011)
  • Author(s): Nakamura S, Tan L, Nagata Y, Takemura T, Asahina A,
  • Journal Title: Mol Carcinog. Volume: in press
  • Peer Reviewed
• [Journal Article] Bcr-Abl-mediated Raf kinase inhibitor protein suppression promotes chronic myeloid leukemia progenitor cells proliferation. (2011)
  • Author(s): Nakamura S, Yagyu T, Takemura T, Tan L, Nagata Y, Yokota
  • Journal Title: Stem Cell Discovery Volume: 1 Pages: 54-66
  • Peer Reviewed
• [Journal Article] Transcriptional Repression of Cdc25B by IER5 Inhibits the Proliferation of Leukemic Progenitor Cells through NF-YB and p300 in Acute Myeloid Leukemia. (2011)
  • Author(s): Nakamura S, Nagata Y, Tan L, Takemura T, Shibata K,
  • Journal Title: PLoS One. Volume: 6
  • Peer Reviewed
• [Journal Article] Small GTPase RAB45-mediated p38 activation in apoptosis of chronic myeloid leukemia progenitor cells. (2011)
  • Author(s): Nakamura S, Takemura T, Tan L, Nagata Y, Yokota D,
  • Journal Title: Carcinogenesis. Volume: 32 Pages: 1758-72
  • Peer Reviewed
• [Journal Article] Down-regulation of thanatos-associated protein 11 by BCR-ABL promotes CML cell proliferation through c-Myc expression. (2011)
  • Author(s): Nakamura S, Yokota D, Tan L, Nagata Y, Takemura T,
  • Journal Title: Int J Cancer. Volume: 31 Pages: 1049-59
  • Peer Reviewed
• [Presentation] Molecular targets of the novel synthesized phospha sugar derivatives, TMPP, and the mechanism of its antileukemic activity (2012)
  • Author(s): Satoki Nakamura, Haruhiko Sugimura
  • Organizer: 第15回国際個別化医療学会
  • Place of Presentation: 東京
  • Year and Date: 2012-11-10
• [Presentation] Molecular targets of the novel synthesized phospha sugar derivatives, TMPP, and the mechanism of its antileukemic activity (2012)
  • Author(s): Satoki Nakamura, Kazuya Shinmura, Haruhiko Sugimura
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] The FOXM1 transcriptional factor promotes the proliferation of leukemia cells through modulation of cell cycle progression in acute myeloid leukemia (2011)
  • Author(s): Satoki Nakamura, Tomonari Takemura, Daisuke Yokota, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Kiyoshi Shibata, Shinya Fujisawa, Kazunori Ohnishi
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] Induction of IER5 inhibits leukemia cell proliferation through modulation of cell cycle progression (2011)
  • Author(s): 中村悟己、竹村兼成、横田大輔、平野功、小野孝明、重野一幸、藤澤紳哉、大西一功
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Roles of RAB45-mediated p38 activation in apoptosis of CML progenitor cells (2011)
  • Author(s): 竹村兼成、中村悟己、横田大輔、平野功、小野孝明、重野一幸、藤澤紳哉、大西一功
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Inhibition of JHDM1B expression suppresses the proliferation of leukemia cells through the cell cycle arrest (2011)
  • Author(s): Lin Tan, Satoki Nakamura, Aya Asahina, Tomonari Takemura, Yasuyuki Nagata, Daisuke Yokota, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Kazunori Ohnishi
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋