The molecular mechanism of prognostic exacerbation by the addition of KIT mutations in CBF leukemia

• Project/Area Number: 22790911
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: FUKUSHIMA Kentaro 大阪大学, 医学系研究科, 助教 (70546879)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: CBF 白血病 / KIT 遺伝子変異 / 薬剤耐性遺伝子 / DNA 修復遺伝子 / CBF白血病 / 予後 / KIT遺伝子 / DNA修復 / KITV814 / CBFβ-MYH11 / レトロウィルス / 白血病 / シグナル伝達 / 肥満細胞腫瘍 / c-Kit遺伝子

Research Abstract

Core binding factor (CBF) acute myeloid leukemia (AML) has a relatively favorable prognosis. However, activating KIT mutations are reported to be associated with higher risk of relapse and shorter survival. This project aims to clarify the molecular mechanism of such unfavorable effects by KIT mutations. The applicant explained that KIT mutations give poor prognosis to CBF leukemia through the induction of drug resistance genes and the reduction of DNA repair-related genes.

Research Products

• [Journal Article] Pulmonary arterial hypertension associated with chronic active Epstein-Barr virus infection (2011)
  • Author(s): Hashimoto T, Fukushima K, Kanakura Y, et al
  • Journal Title: Intern Med Volume: 50:119-124
  • NAID: 130000413209
  • Peer Reviewed
• [Journal Article] Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells (2011)
  • Author(s): Fujita J, Fukushima K, Kanakura Y, et al
  • Journal Title: Immunol Lett Volume: 136:61-73
  • Peer Reviewed
• [Journal Article] Pulmonary Arterial Hypertension Associated with Chronic Active Epstein-Barr Virus Infection (2011)
  • Author(s): Hashimoto T, Fukushima K, et.al.
  • Journal Title: Internal Medicine Volume: 50 Issue: 2 Pages: 119-124
  • DOI: 10.2169/internalmedicine.50.4143
  • NAID: 130000413209
  • ISSN: 0918-2918, 1349-7235
  • Peer Reviewed
• [Journal Article] Myeloid neoplasm-related gene abnormalities differentially affect dendritic cell differentiation from murine hematopoietic stem/progenitor cells (2011)
  • Author(s): Fujita J, Mizuki M, Otsuka M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Tokunaga M, Matsumura I, Kanakura Y
  • Journal Title: Immunology letters Volume: 138 Issue: 1 Pages: 61-73
  • DOI: 10.1016/j.imlet.2010.12.006
  • Peer Reviewed
• [Journal Article] BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Ras signal by inducing p21CIP1/WAF1 (2010)
  • Author(s): Tokunaga M, Ezoe S, Fukushima K, et al
  • Journal Title: J Biol Chem. Volume: 285:31774-31782
  • Peer Reviewed
• [Journal Article] BCR-ABL but not JAK2 V617F inhibits erythropoiesis through the Rassignal by inducing p21CIP1/WAF1. (2010)
  • Author(s): Tokunaga M, Ezoe S, Tanaka H, Satoh Y, Fukushima K, Matsui K, Shibata M, Tanimura A, Oritani K, Matsumura I, Kanakura Y.
  • Journal Title: Journal of Biological Chemistry Volume: 285 Pages: 31774-31782
  • Peer Reviewed
• [Presentation] 5.0mg/kg のサイモグロブリン[〇!R](rATG, Genzyme) を前処置に用いた同種造血幹細胞移植における感染症についての検討 (2012)
  • Author(s): 佐多 弘 ほか
  • Organizer: 第34回日本造血細胞移植学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2012-02-25
• [Presentation] 同種造血細胞移植におけるATG(サイモグロブリン[○!R])投与後のEBウイルス再活性化・LPDの発症の検討 (2011)
  • Author(s): 福島健太郎、金倉譲, 等
  • Organizer: 第73回日本血液学会
  • Place of Presentation: 愛知県名古屋市
  • Year and Date: 2011-10-16
• [Presentation] 同種造血細胞移植における ATG(サイモグロブリン)投与後のEB ウイルス再活性化・ LPD の発症の検討 (2011)
  • Author(s): 福島健太郎 ほか
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 愛知
• [Presentation] 当科における悪性リンパ腫に対する DeVIC 療法施行例の後方視的検討 (2011)
  • Author(s): 大塚正恭 ほか
  • Organizer: 第9回日本臨床腫瘍学会学術集会
  • Place of Presentation: 神奈川
• [Presentation] 再生不良性貧血に対しrATG(サイモグロブリン)を用いた前処置にて施行した同種骨髄移植の検討 (2011)
  • Author(s): 佐多 弘 ほか
  • Organizer: 第33回日本造血細胞移植学会総会
  • Place of Presentation: 愛媛
• [Presentation] 骨髄性悪性疾患に対する FLU/BU/MEL を前処置とした造血幹細胞移植 (2011)
  • Author(s): 福島健太郎 ほか
  • Organizer: 第33回日本造血細胞移植学会総会
  • Place of Presentation: 愛媛
• [Presentation] 血液悪性腫瘍に対する同種造血幹細胞移植の前処置における減量 rATG (rabbit antithymocyte globulin)の影響 (2011)
  • Author(s): 前田哲生 ほか
  • Organizer: 第33回日本造血細胞移植学会総会
  • Place of Presentation: 愛媛
• [Presentation] Leukemia-related gene abnormalities affect steady-state dendritic cell differentiation(非炎症状態の樹状細胞分化における白血病関連遺伝子異常の役割) (2011)
  • Author(s): 藤田二郎 ほか
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
• [Presentation] Myeloid neoplasm-related gene abnormalities differentially affect FLT3-ligand mediated dendritic cell differentiation from murine hematopoietic stem/progenitor cells (2010)
  • Author(s): Fujita J, et al
  • Organizer: The American Society of Hematology 52nd Annual Meeting
  • Place of Presentation: Orlando, USA
• [Presentation] Leukemia-related gene abnormalities affect FLT3-ligand-mediated dendritic cell differentiation (2010)
  • Author(s): 藤 田二郎 ほか
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 神奈川
• [Presentation] Detection of patient specific MRD with quantitive RT PCR in the patients with Multiple Myeloma
  • Author(s): H.SATA, K.FUKUSHIMA, et al.
  • Organizer: 14th International Myeloma Workshop
  • Place of Presentation: 京都府・京都国際会館
• [Presentation] 生着不全の経過を持つ治療抵抗性AML/MDS症例に対し、採取量不十分な非血縁者骨髄に臍帯血を加えた複数造血幹細胞移植を施行した一例
  • Author(s): 山下 由紀子、福島 健太郎、ほか
  • Organizer: 第35回日本造血細胞移植学会総会
  • Place of Presentation: 石川県・石川県立音楽堂ほか
• [Remarks] 第17回ヨーロッパ血液学会(EHA)年次総会EHA-JSH fellowship exchange program award 2012.6.15
• [Remarks] ホームページ
  • URL: http://www.med.osaka-u.ac.jp/pub/bldon/www/home.html