Functional analysis of miRNA/transcription factors highly expressed in leukemia stem cells

• Project/Area Number: 20591134
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: TAKENAKA Katsuto Kyushu University, 大学病院, 助教 (30301295)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 白血病幹細胞 / 造血幹細胞 / 遺伝子プロファイル / miRNA / 転写因子

Research Abstract

Normal hematopoiesis and acute myeloid leukemia are organized as hierarchies with stem cells, which possess extensive self-renewal and proliferative capacity. We identified a core transcriptional program shared by normal and leukemia stem cells, revealing the molecular machinery underlying stemness properties. Biological derteminants of stemness influence clinical outcome of leukemia, and are potential targets for novel therapy.

Research Products

• [Journal Article] TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. (2010)
  • Author(s): Kikushige Y
  • Journal Title: Cell Stem Cell 7 Pages: 708-717
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. (2010)
  • Author(s): Oku S, Takenaka K
  • Journal Title: Br J Haematol 150 Pages: 334-344
• [Journal Article] TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. (2010)
  • Author(s): Kikushige Y, et al
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 708-717
  • Peer Reviewed
• [Journal Article] JAK2 V617F uses distinct signalling pathways to induce cell proliferation and neutrophil activation. (2010)
  • Author(s): Oku S, et al
  • Journal Title: Br J Haematol Volume: 150 Pages: 334-344
  • Peer Reviewed
• [Journal Article] Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma : retrospective analysis of the experience of the Fukuoka BMT group. (2010)
  • Author(s): Numata A, et al
  • Journal Title: Bone Marrow Transplant Volume: 45 Pages: 311-316
  • Peer Reviewed
• [Journal Article] High incidence of false-positive Aspergillus galactomannan test in multiple myeloma. (2010)
  • Author(s): Mori Y, et al
  • Journal Title: Am J Hematol Volume: 85 Pages: 449-451
  • Peer Reviewed
• [Journal Article] High incidence of HHV6-associated encephalitis/myelitis following a second unrelated cord blood transplantation. (2010)
  • Author(s): Mori Y, et al
  • Journal Title: Biol Blood Marrow Transplant Volume: 16 Pages: 1596-1602
  • Peer Reviewed
• [Journal Article] Successful treatment of refractory advanced nasal NK/T cell lymphoma with unrelated cord blood stem cell transplantation incorporating focal irradiation. (2010)
  • Author(s): Mori Y, et al
  • Journal Title: Int J Hematol Volume: 91 Pages: 107-111
  • Peer Reviewed
• [Journal Article] Cord blood stem cell transplantation in a patient with disseminated mucormycosis and acute myelogenous leukemia. (2010)
  • Author(s): Aoki T, et al
  • Journal Title: Transpl Infect Dis Volume: 12 Pages: 277-279
  • Peer Reviewed
• [Journal Article] Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma : retrospective analysis of the experience of the Fukuoka BMT group (2010)
  • Author(s): Numata A, et al
  • Journal Title: Bone Marrow Transplant 45(印刷中)
  • Peer Reviewed
• [Journal Article] Identification of the human eosinophil lineage-committed progenitor : revision of phenotypic definition of the human common myeloid progenitor. (2009)
  • Author(s): Mori Y
  • Journal Title: J Exp Med 206 Pages: 183-193
• [Journal Article] FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation. (2009)
  • Author(s): Yoshimoto G
  • Journal Title: Blood 114 Pages: 5034-5043
• [Journal Article] FLT3-ITD upregulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation (2009)
  • Author(s): Yoshimoto G, et al
  • Journal Title: Blood 114 Pages: 5034-5043
  • Peer Reviewed
• [Journal Article] The impact of cytogenetic abnormalities on the prognosis of primary myelofibrosis : a prospective survey of 202 cases in Japan (2009)
  • Author(s): Hidaka T, et al
  • Journal Title: Eur J Haematol 83 Pages: 328-333
  • Peer Reviewed
• [Journal Article] Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease (2009)
  • Author(s): Teshima T, et al
  • Journal Title: Int J Hematol 90 Pages: 253-260
  • Peer Reviewed
• [Journal Article] Second unrelated cord blood transplantation using a reduced-intensity conditioning regimen combined with gemtuzumab ozogamicin in patients with relapsed acute myelogenous leukemia (2009)
  • Author(s): Yamauchi T, et al
  • Journal Title: Int J Hematol 90 Pages: 416-420
  • Peer Reviewed
• [Journal Article] Efficacy and feasibility of IDEA therapy for refractory or relapsed non-Hodgkin's lymphoma (2009)
  • Author(s): Nishimori, et al
  • Journal Title: Anticancer Res 29 Pages: 1749-1754
  • Peer Reviewed
• [Journal Article] Infectious' complications in patients receiving autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases (2009)
  • Author(s): Kohno K, et al
  • Journal Title: Transpl Infect Dis 11 Pages: 318-323
  • Peer Reviewed
• [Journal Article] Identification of the human eosinophil lineage-committed progenitor : revision of phenotypic definition of the human common myeloid progenitor. (2009)
  • Author(s): Mori Y, et al
  • Journal Title: J Exp Med 206 Pages: 183-193
  • Peer Reviewed
• [Journal Article] Oral valganciclovir as preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients. (2009)
  • Author(s): Takenak K, et al
  • Journal Title: Int J Hematol (印刷中)
  • Peer Reviewed
• [Journal Article] Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. (2008)
  • Author(s): Shide K
  • Journal Title: Leukemia 22 Pages: 87-95
• [Journal Article] Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. (2008)
  • Author(s): Kikushige Y
  • Journal Title: J Immunol 180 Pages: 7358-7367
• [Journal Article] Human Flt3 is expressed at the hematopoietic stem cell and the granulocyte/macrophage progenitor stages to maintain cell survival. (2008)
  • Author(s): Kikushige Y, et al
  • Journal Title: J Immunol 180 Pages: 7358-7367
  • Peer Reviewed
• [Journal Article] Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. (2008)
  • Author(s): Shide K, et al
  • Journal Title: Leukemia 22 Pages: 87-95
  • Peer Reviewed
• [Journal Article] Stem cell gene expression programs influence clinical outcome in human leukemia.
  • Author(s): Eppert K, Takenaka K
  • Journal Title: Nat Med (in press).
• [Presentation] Enriched micro RNA-126 bioactivity marks the primitive compartment in AML and regulates LSC numbers. (2010)
  • Author(s): Lechman E, et al.
  • Organizer: 第52回米国血液学会
  • Place of Presentation: オーランド,米国
  • Year and Date: 2010-12-05
• [Presentation] Enriched microRNA-126 bioactivity marks the primitive compartment in AML and regulates LSC numbers (2010)
  • Author(s): Lechman E, et al
  • Organizer: 第52回米国血液学会
  • Place of Presentation: オーランド,米国
  • Year and Date: 2010-12-05
• [Presentation] Prognostic impact of cytogenetic abnormalities in primary myelofibrosis : prospective survey in Japan. (2010)
  • Author(s): Shide K, et al.
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] New immunodeficient mouse model for human HSC assay introduced defined sirpa polymorphism (2010)
  • Author(s): Urata S, et al
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] A novel fusion partner of PDGFRA identified in chronic eosinophilic leukemia (2010)
  • Author(s): Kohno K, et al
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] Prognostic impact of cytogenetic abnormalities in primary myelofibrosis : prospective survey in Japan (2010)
  • Author(s): Shide K, et al
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] A new immunodeficient mouse model introduced with defined Sirpa polymorphism for human hematopoietic stem cell assay. (2010)
  • Author(s): Urata S, et al.
  • Organizer: 第39回国際血液・幹細胞学会議(ISEH)
  • Place of Presentation: メルボルン,オーストラリア
  • Year and Date: 2010-09-16
• [Presentation] A new immunodeficient mouse model introduced with defined Sirpa polymorphism for human hematopoietic stem cell assay (2010)
  • Author(s): Urata S, et al
  • Organizer: 第39回国際血液・幹細胞学会議(ISEH)
  • Place of Presentation: メルボルン,オーストラリア
  • Year and Date: 2010-09-16
• [Presentation] Leukemic and Normal Stem Cell Transcriptional Signatures Determined by Functional Assays Are Predictive of the Overall Survival of AML Patients. (2009)
  • Author(s): Eppert K, et al.
  • Organizer: 第51回米国血液学会
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2009-12-07
• [Presentation] Leukemic and Normal Stem Cell Transcriptional Signatures Determined by Functional Assays Are Predictive of the Overall Survival of AML Patients (2009)
  • Author(s): Eppert K, et al
  • Organizer: 第51回米国血液学会
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2009-12-07
• [Presentation] JAK2V617F mutation selectively exerts the STAT3 pathway for enhancing a neutrophil activation marker. (2009)
  • Author(s): Oku S, et al.
  • Organizer: 第51回米国血液学会
  • Place of Presentation: ニューオーリンズ,米国
  • Year and Date: 2009-12-05
• [Presentation] JAK2V617F mutation selectively exerts the STAT3 pathway for enhancing a neutrophil activation marker (2009)
  • Author(s): Oku S, et al
  • Organizer: 第51回米国血液学会
  • Place of Presentation: ニューオーリンズ、米国
  • Year and Date: 2009-12-05
• [Presentation] Human SIRPA polymorphism modulates macrophagemediated suppression of humanhematopoiesis. (2009)
  • Author(s): Kuriyama T, et al.
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都.
  • Year and Date: 2009-10-23
• [Presentation] Human SIRPA polymorphism modulates macrophage-mediated suppression of human hematopoiesis (2009)
  • Author(s): Kuriyama T, et al
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] Elevated neutrophil alkaline phophatase scores induced by Jak2 V617F mutation via Stat3 (2009)
  • Author(s): Oku S, et al
  • Organizer: 第71回日本血液学会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23
• [Presentation] Human SIRPA polymorphism modulates macrophage-mediated suppression of human hematopoiesis (2009)
  • Author(s): Kuriyama T, et al
  • Organizer: The 7^<th> Stem Cell Research Symposium
  • Place of Presentation: 東京
  • Year and Date: 2009-05-15
• [Presentation] High levels of microRNA-126 bioactivity specify the LSC compartment in AML. (2008)
  • Author(s): Lechman E, et al.
  • Organizer: 第50回米国血液学会
  • Place of Presentation: サンフランシスコ,米国
  • Year and Date: 2008-12-09
• [Presentation] High levels of microRNA-126 bioactivity specify the LSC compartment in AML. (2008)
  • Author(s): Lechman E, et al
  • Organizer: 第50回米国血液学会
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2008-12-09
• [Presentation] Human SIRPA polymorphism modulates macrophagemediated suppression of human hematopoiesis. (2008)
  • Author(s): Kuriyama T, et al.
  • Organizer: 第50回米国血液学会
  • Place of Presentation: サンフランシスコ,米国
  • Year and Date: 2008-12-08
• [Presentation] Human SIRPA polymorphism modulates macrophage-mediated suppression of human hematopoiesis. (2008)
  • Author(s): Kuriyama T, et al
  • Organizer: 第50回米国血液学会
  • Place of Presentation: サンフランシスコ、米国
  • Year and Date: 2008-12-08
• [Presentation] Identification and characterization of regulatory networks specific for leukemia stem cells. (2008)
  • Author(s): Eppert K, et al
  • Organizer: 第73回Cold Spring Harbor Lab シンポジウム
  • Place of Presentation: Cold Spring Harbor, 米国
  • Year and Date: 2008-05-28
• [Patent(Industrial Property Rights)] LSC and HSC signatures for predicting survival of patients having hematological cancer. (2009)
  • Inventor(s): Dick JE, 他9名
  • Industrial Property Rights Holder: Dick JE, 他9名
  • Filing Date: 2009-12-04
• [Patent(Industrial Property Rights)] LSC and HSC signatures for predicting survival of patients having hematological cancer (2009)
  • Inventor(s): Dick J, et al
  • Industrial Property Rights Holder: Dick J, et al
  • Filing Date: 2009-12-04
  • Overseas