Investigation of the novel mechanisms regulating AML/Runx1

• Project/Area Number: 22790298
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University (2012-2013); Kyoto Prefectural University of Medicine (2010-2011)
• Principal Investigator: YOKOTA Asumi 京都大学, 医学(系)研究科(研究院), 研究員 (00571556)
• Project Period (FY): 2010-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: Runx1 / 翻訳後修飾 / 転写因子 / 造血

Research Abstract

There are nine serine/threonine residues in the C-terminal region of mouse Runx1, which are capable of being phosphorylated. We have made two Runx1 mutants; Dephospho-mimetic 1-9A and phospho-mimetic 1-9D mutant, of which all of these serine/threonine residues were mutated to alanine or aspartic acid, respectively. In luciferase assay, transcriptional activities of these mutants were affected compared with WT Runx1. However, protein expression levels or intracellular localizations were not changed.
Next we have established Runx1 mutant-KI ES cells. 1-9A or 1-9D mutant has been knocked-in to Runx1-KO ES cells. Both 1-9A and 1-9D KI ES cells could differentiate toward hematopoietic cells, indicating that these mutants retain their activity, which could rescue the differentiation blockade of Runx1 KO ES cells. As the frequencies of hematopoietic colonies were affected by these mutations, it is suggested that phosphorylation status of Runx1 might regulate its biological activity.

Research Products

• [Journal Article] 造血発生制御メカニズムの今日的理解 (2010)
  • Author(s): 横田明日美, 奥田 司
  • Journal Title: 京都府立医科大学雑誌 Volume: 119(10) Pages: 681-693
• [Journal Article] 造血発生制御メカニズムの今日的理解 (2010)
  • Author(s): 横田明日美、奥田司
  • Journal Title: 京都府立医科大学雑誌 Volume: 119 Pages: 681-693
• [Presentation] 間葉系幹細胞と副甲状腺ホルモンを応用した造血細胞の増幅. (O26-1) (2014)
  • Author(s): 三浦康生, 八尾尚幸, 吉岡 聡, 岩佐磨佐紀, 田村彰広, 佐藤 淳, 横田明日美, 平位秀世, 一戸辰夫, 前川 平
  • Organizer: 第36回日本造血細胞移植学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 2014-03-08
• [Presentation] Direct Interaction with Bone Marrow Mesenchymal Stromal/Stem Cells Is Required for Hematopoietic Expansion by Parathyroid Hormone. [Abstract #3689] (2013)
  • Author(s): Yao H, Miura Y, Yoshioka S, Iwasa M, Sato A, Tamura A, Yokota A, Ashihara E, Ichinohe T, Hirai H,Maekawa T
  • Organizer: American Society of Hematology, 55th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-09
• [Presentation] Hypoxia-Adapted Myeloma Cells Possess Stem Cell Character. [Abstract #3088] (2013)
  • Author(s): Ashihara E, Nakagawa Y, Yao H, Yokota A, Miura Y, Takata K, Kitamura Y, Hirai H , Maekawa T
  • Organizer: American Society of Hematology, 55th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-08
• [Presentation] Cytokine-STATs signalings upregulate endogenous C/EBPβ in BCR-ABL+ leukemic cells independently from BCR-ABL signaling. [Abstract #1468] (2013)
  • Author(s): Yokota A, Hirai H, Hayashi Y, Tamura A, Sato A, Yao H, Yoshioka S, Iwasa M, Ashihara E, Miura Y, Maekawa T
  • Organizer: American Society of Hematology, 55th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-07
• [Presentation] Cell-intrinsic and -extrinsic involvement of C/EBPβ in the regulation of hematopoietic stem cells. [Abstract #1202] (2013)
  • Author(s): Tamura A, Hirai H, Hayashi Y, Yokota A, Sato A, Yao H, Yoshioka S, Iwasa M, Ashihara E, Miura Y, Maekawa T
  • Organizer: American Society of Hematology, 55th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-07
• [Presentation] C/EBPβ expressed by bone marrow mesenchymal stromal cells is indispensable for precursor B-cell lymphopoiesis. [Abstract #1213] (2013)
  • Author(s): Yoshioka S, Miura Y, Yao H, Iwasa M, Sato A, Tamura A, Yokota A, Hishita T, Ichinohe T, Hirai H, Maekawa T
  • Organizer: American Society of Hematology, 55th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2013-12-07
• [Presentation] Proliferation and differentiation of hematopoietic cells by osteogenic-induced bone marrow MSCs (2013)
  • Author(s): Yao H, Miura Y, Yoshioka S, Iwasa M, Sato A, Hayashi Y, Tamura A, Yokota A, Ichinohe T, Tohyama K, Hirai H, Maekawa T
  • Organizer: The 75th Annual Meeting of the Japanese Society of Hematology(Jpn J Clin Hematol. 2013; 54 : 346, OS-2-113)
  • Place of Presentation: Sapporo
  • Year and Date: 2013-10-12
• [Presentation] Involvement of C/EBPβ in the regulation of hematopoietic stem cells (2013)
  • Author(s): Tamura A, Hirai H, Hayashi Y, Yokota A, Yao H, Yoshioka S, Sato A, Iwasa M, Ashihara E, Miura Y, and Maekawa T.
  • Organizer: The 75th Annual Meeting of the Japanese Society of Hematology(Jpn J Clin Hematol. 2013; 54 : 437, PS-1-2)
  • Place of Presentation: Sapporo
  • Year and Date: 2013-10-11
• [Presentation] 転写因子C/EBPβは骨髄系分化・増殖の誘導によりCML幹細胞を減少させる (2013)
  • Author(s): 林 嘉宏, 平位秀世, 横田明日美, 八尾尚幸, 三浦康生, 芦原英司, 前川 平
  • Organizer: 第17回日本がん分子標的治療学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2013-06-13
• [Presentation] Parathyroid hormone enhances expansion through CDH11 in human bone marrow mesenchymal stromal/stem cells (2013)
  • Author(s): Yao H, Miura Y, Yoshioka S, Hayashi Y, Yokota A, Tamura A, Ichinohe T, Hirai H and Maekawa T.
  • Organizer: AsiaCORD 2013 , Scientific Symposium I-1 "New Insights into Stem Cell Biology- Stem Cell Development & Differentiation"
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2013-04-19
• [Remarks] 京都大学医学部附属病院輸血細胞治療部HP
  • URL: http://dtm.kuhp.kyoto-u.ac.jp
• [Remarks] 京都大学医学部附属病院輸血細胞治療部
  • URL: http://dtm.kuhp.kyoto-u.ac.jp