Analysis of the mechanisms of RUNX1 gene regulation in the pathogenesis of leukemia

• Project/Area Number: 20591114
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: University of Yamanashi
• Principal Investigator: SAKOE Kumi University of Yamanashi, 医学部, ポストドクター (10398505)
• Co-Investigator(Kenkyū-buntansha): KOMATU Norio 順天堂大学, 医学部, 教授 (50186798) ; 桐戸 敬太 山梨大学, 大学院・医学工学総合研究部, 教授 (90306150)
• Co-Investigator(Renkei-kenkyūsha): KIRITO Keita 山梨大学, 大学院・医学工学総合研究部, 教授 (90306150)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: RUNX1 / 家族性血小板減少症 / 白血球 / 遺伝子変異 / 発現調節 / 家族性血小板機能異常症 / 白血病

Research Abstract

RUNX1 is a transcription factor that is essential for hematopoiesis and is the causative gene of the familial platelet disorder that developing leukemia in a high risk. SNP in the promoter region of RUNX1 gene effects on the RUNX1 transcription, and allelic imbalance causes the over-expression of mutation transcript in the same allele at SNP. New 4 lysine residues in the carboxyl terminal of mutant RUNX1 protein that differs from normal RUNX1 due to a frame shift mutation are target of ubiquitination and degradation. It was suggested that the allelic expression imbalance and a decrease of protein level cause the risk of leukemia.

Research Products

• [Journal Article] NF-κB mediates aberrant activation of HIF-1 in malignant lymphoma (2010)
  • Author(s): Qiao Q, Nozaki Y, Sakoe K, Komatsu N, Kirito K.
  • Journal Title: Exp Hematol 38 Pages: 1199-1208
  • Peer Reviewed
• [Journal Article] FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia (2010)
  • Author(s): Sakoe Y, Sakoe K, Kirito K, Ozawa K, Komatsu N.
  • Journal Title: Blood 115 Pages: 3787-95
  • Peer Reviewed
• [Journal Article] NF-κB mediates aberrant activation of HIF-1 in malignant lymphoma (2010)
  • Author(s): Qiao Q
  • Journal Title: Exp Hematol. Volume: 38 Pages: 1199-1208
  • Peer Reviewed
• [Journal Article] FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia (2010)
  • Author(s): Sakoe Y
  • Journal Title: Blood Volume: 115 Pages: 3787-3795
  • Peer Reviewed
• [Journal Article] FOXO3A as a key molecule for all-trans retinoic acid-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia. (2010)
  • Author(s): Sakoe Y
  • Journal Title: Blood (in press)
  • Peer Reviewed
• [Journal Article] Adult-onset Alexander disease with typical"tadpole"brainstem atrophy and unusual bilateral basal ganglia involvement : a case report and review of the literature t (2010)
  • Author(s): Namekawa M
  • Journal Title: BMC Neurology (in press)
  • Peer Reviewed
• [Journal Article] Inhibition of HIF-1 function enhances the sensitivity of multiple myeloma cells to melphalan (2009)
  • Author(s): ongzhen Hu, Kirito K, Yoshida K, Mitsumori T, Nakajima K, Nozaki Y, Hamanaka S, Nagashima T, Kunitama M, Sakoe K, Komatsu N.
  • Journal Title: Molecular cancer therapeutics 8 Pages: 2329-2338
  • Peer Reviewed
• [Journal Article] Familial sideroblastic anemia associated with cardiac atrial septal defect. (2009)
  • Author(s): Mori M, Nakamoto S, Akifuji Y, Tanaka T, Komatsu N, Hatake K, Ozawa K.
  • Journal Title: Am J Hematol 7 Pages: 451-452
  • Peer Reviewed
• [Journal Article] HIF-1 prevents the overproduction of mitochondrial ROS after cytokine stimulation through induction of PDK-1 (2009)
  • Author(s): Kirito K, Hu Y, Komatsu N.
  • Journal Title: Cell cycle 8 Pages: 2844-2849
  • Peer Reviewed
• [Journal Article] Inhibition of hypoxia-inducible factor-1 function enhances the sensiti vity of multiple myeloma cells to melphalan (2009)
  • Author(s): Hu Y
  • Journal Title: Molecular cancer therapeutics 8 Pages: 2329-2338
  • Peer Reviewed
• [Journal Article] Thrombopoietin (TPO) regulates HIF-1a levels through generation of mitochondrial reactive oxygen species. (2008)
  • Author(s): Yoshida K, Kirito K, Yongzhen H, Ozawa K, Kaushansky K, Komatsu N.
  • Journal Title: Int J Hematol 88 Pages: 43-51
  • Peer Reviewed
• [Journal Article] A novel RUNX1 mutation in familial platelet disorder with propensity to develop myeloid malignancies. (2008)
  • Author(s): Kirito K, Sakoe K, Shinoda D, Takiyama Y, Kaushansky K, Komatsu N
  • Journal Title: Haematologica 93 Pages: 155-156
  • Peer Reviewed
• [Presentation] Impact of Protein Phosphatase PP2A on ATRA-Induced Activation of FoxO3a In Acute Promyelocytic Leukemia Cells (2010)
  • Author(s): 迫江公己, 他
  • Organizer: ASH Annual Meeting and Exposition
  • Place of Presentation: ORLAND, FL
  • Year and Date: 2010-12-05
• [Presentation] RUNX1 の発現調節異常による白血病発症のメカニズムの解析 (2008)
  • Author(s): 桐戸敬太、迫江公己, 他
  • Organizer: 日本臨床血液学会総会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Presentation] RUNX1の発現調節異常による白血病発症のメカニズムの解析. (2008)
  • Author(s): 桐戸敬太
  • Organizer: 日本臨床血液学会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-11
• [Book] Heat Shock Proteins : New Research, Nova Science (2008)
  • Author(s): Kumi Sakoe, Yoshihisa Takiyama
  • Total Pages: 513
  • Publisher: Publishers
• [Book] Heat Shock Proteins : New Research (2008)
  • Author(s): Kumi Sakoe
  • Total Pages: 513
  • Publisher: Nova Science Publishers
• [Remarks]
  • URL: http://www.yamanashi-hematology.com/
• [Remarks]
  • URL: http://www.yamanashi-hematology.com/