Analysis of mechanisms in hematopoietic regulation by transcription factors

• Project/Area Number: 20390275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Dokkyo Medical University
• Principal Investigator: MITANI Kinuko Dokkyo Medical University, 医学部, 教授 (50251244)
• Co-Investigator(Kenkyū-buntansha): 牧 和宏 獨協医科大学, 医学部, 講師 (50337391) ; 佐々木 光 獨協医科大学, 医学部, 講師 (60282638) ; 中村 由香 獨協医科大学, 医学部, 講師 (80364595) ; 山形 哲也 獨協医科大学, 医学部, 准教授 (30424047)
• Project Period (FY): 2008 – 2012
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2010: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2009: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: TEL / RUNX1 / EVI1 / microRNA / MIR9 / ES / マウス / 白血病 / MIR-9 / UT-7/GM / エリスロポエチン / ベンチジン / β-グロビン / ALAS-E / glvcophorin A / miR-9 / AML / Taqman法 / 定量PCR法 / 全生存 / 予後不良 / MDS / miRNA / レポーター・アッセイ

Research Abstract

12p13及び21q22転座型白血病の発症機構を解明することを目的に、転座標的遺伝子TEL及びRUNX1の機能と機能制御機構を解析するとともに、キメラ遺伝子の機能を明らかにする。
(1)野生型TELの機能制御機構を翻訳後修飾の観点から解析する。
(2)野生型TELの機能をノックアウト及びトランスジェニックES細胞を用いて、in vitro及びマウス個体で解析する。
(3)野生型RUNX1の翻訳制御機構をmicroRNAレベルで解析する。
(4)RUNX1/EVI1の標的遺伝子を同定する。

Research Products

• [Journal Article] 骨髄異形成症候群(MDS)関連遺伝子 (2011)
  • Author(s): 牧和宏、三谷絹子
  • Journal Title: 血液フロンティア 21 Pages: 109-116
• [Journal Article] 骨髄異形成症候群(MDS)関連遺伝子 (2011)
  • Author(s): 牧和宏
  • Journal Title: 血液フロンティア Volume: 21 Pages: 109-116
• [Journal Article] 骨髄異形成症候群の染色体・遺伝子異常と予後 (2010)
  • Author(s): 中村由香、三谷絹子
  • Journal Title: 血液・腫瘍科 61 Pages: 398-402
• [Journal Article] Multicenter phase II trial of vitamine K2 plus 1 a-hydroxyvitamine D3 combination therapy for low-risk myelodysplastic syndrome. (2010)
  • Author(s): Akiyama N
  • Journal Title: Leuk Res Volume: 34 Pages: 1151-1157
  • Peer Reviewed
• [Journal Article] Prognostic potential of detection of WT1 mRNA level in peripheral blood in adult acute myeloid leukemia. (2010)
  • Author(s): Miyawaki S
  • Journal Title: Leuk & Lymph Volume: 51 Pages: 1855-1861
  • Peer Reviewed
• [Journal Article] Enhanced expression of the EVI1 gene in NUP98/HOXA-expressing leukemia cells. (2009)
  • Author(s): Eguchi-Ishimae M, Eguchi M, Ohyashiki K, Yamagata T, Mitani K
  • Journal Title: Int J Hematol 89 Pages: 253-256
  • NAID: 10025160451
  • Peer Reviewed
• [Journal Article] Leukaemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates haemoglobin synthesis. (2009)
  • Author(s): Eguchi-Ishimae M, Eguchi M, Maki K, Porcher C, Shimizu R, Yamamoto M, Mitani K.
  • Journal Title: Cancer Sci 100 Pages: 689-697
  • Peer Reviewed
• [Journal Article] Enhanced expression of the EVI1 gene in NUP98/HOXA-expressing leukemia cells (2009)
  • Author(s): Eguchi-Ishimae M
  • Journal Title: Int J Hematol 89 Pages: 253-256
  • Peer Reviewed
• [Journal Article] Leukaemia-related transcription factor TEL/ETV6 expands erythroid precursors and stimulates haemoglobin synthesis (2009)
  • Author(s): Eguchi-Ishimae M
  • Journal Title: Cancer Sci 100 Pages: 689-697
  • Peer Reviewed
• [Journal Article] I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia : Final results of Japanese multi-center cooperative study (2009)
  • Author(s): Kobayashi Y
  • Journal Title: Int J Hematol 90 Pages: 91-93
  • Peer Reviewed
• [Journal Article] Enhanced expression of the EVI1 gene in NUP98/HOXA-expressing leukemia cells. (2009)
  • Author(s): Eguchi-Ishimae M
  • Journal Title: Int J Hematol 89 Pages: 253-256
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitors trichostatin A and valproic acid circumvent apoptosis in human leukemic cells expressing the RUNX1 chimera. (2008)
  • Author(s): Sasaki K, Yamagata T, Mitani K
  • Journal Title: Cancer Sci 99 Pages: 414-422
  • NAID: 10024002884
  • Peer Reviewed
• [Journal Article] Role of the RUNX1-EVI1 fusion gene in leukemogenesis. (2008)
  • Author(s): Maki K
  • Journal Title: Cancer Sci 99 Pages: 1878-1883
  • NAID: 10024011504
  • Peer Reviewed
• [Journal Article] Leukaemia-related transcription factor TEL/ETV6 expandsoherythroid precursors and stimulates haemoglobin synthesis.
  • Author(s): Eguchi-Ishimae M
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Presentation] Dysregulated gene and microRNA expression of MDS. (2011)
  • Author(s): Maki K, Mitani K.
  • Organizer: JSH International Symposium 2011 in Nagasaki.
  • Place of Presentation: 長崎
  • Year and Date: 2011-04-23
• [Presentation] Molecular pathogenesis of MDS and its clinical implication. (2010)
  • Author(s): Maki K, Sasaki K, Yamagata T, Mitani K.
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-26
• [Presentation] Abnormal expression of mir-9 indicates poor prognosis in AML patients. (2010)
  • Author(s): Maki K, Yamagata T, Sasaki K, Mitani K.
  • Organizer: 15^<th> Congress of EHA.
  • Place of Presentation: Barcelona
• [Presentation] High expression of microRNA-9 is a hallmark for poor prognosis in acute leukemia patients. (2009)
  • Author(s): Yamagata T, Sasaki K, Maki K, Mitai K.
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] High expression of microRNA-9 is a hallmark for poor prognos is in acute leukemia patients (2009)
  • Author(s): Yamagata T
  • Organizer: 第71回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] 白血病関連転写因子のmicroRNAによる制御 (2008)
  • Author(s): 山形哲也、三谷絹子
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] microRNAによるTELの発現制御機構の解析およびMDS発症への関与の検討 (2008)
  • Author(s): 佐々木光
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
• [Presentation] MDS症例におけるmicroRNAの発現解析 (2008)
  • Author(s): 山形哲也
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10