Isolation of novel class I mutation in infantile acute myeloid

• Project/Area Number: 21591344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hirosaki University
• Principal Investigator: TOKI Tsutomu 弘前大学, 大学院・医学研究科, 講師 (50195731)
• Co-Investigator(Kenkyū-buntansha): 渡邉 誠二 弘前大学, 大学院・医学研究科, 助教 (10241449)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白血病 / 転写因子 / ダウン症 / 一過性骨髄増殖症 / GATA1 / 乳児急性骨髄性白血病 / 一過性骨髄異常増殖症

Research Abstract

Neonates with Down syndrome (DS) are at a high risk of developing transient abnormal myelopoiesis (TAM) and myeloid leukemia in DS (ML-DS). Most cases with both disorders carry somatic GATA1 mutations. This mutation results in the exclusive expression of a truncated protein lacking the N-terminal 83 amino acids (GATA1s). We tried to isolation of novel class I mutation from these disorders, but unfortunately we could not execute the object. Here, we report naturally occurring GATA1 mutants with internal deletions of 15 or 43 amino acids (GATA1 ID) observed in six patients with TAM, which were caused by abnormal alternative splicing due to the mutations in exon 3. WBC counts of all patients have the mutations were extremely high. These results indicated that the mutations have class 1 like activity

Research Products

• [Journal Article] Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia (2012)
  • Author(s): Takashi Yokoyama, Tsutomu TokiTakashi Yokoyama, Tsutomu Toki, Yoshihiro Aoki, Rika Kanezaki, Myoung-ja Park, Yohei Kanno, Myoung-ja Park, Yohei Kanno, Etsuro Ito, Yasuhide Hayashi, Takuro Nakamura
  • Journal Title: Blood Volume: 119(11) Pages: 208-2611
  • Peer Reviewed
• [Journal Article] Down syndrome and GATA1 mutations in transient abnormal myeloproliferative disorder : mutation classes correlate with progression to myeloid leukemia (2010)
  • Author(s): Rika Kanezaki, Tsutomu Toki, Kiminori Terui, Gang Xu, RuNan Wang, Akira Shimada, Asahito Hama, Hirokazu Kanegane, Kiyoshi Kawakami, Mikiya Endo, Daisuke Hasegawa, Kazuhiro Kogawa, Souichi Adachi, Yasuhiko Ikeda, Shotaro Iwamoto, Takashi Taga, Yoshiyuki Kosaka, Seiji Kojima, Yasuhide Hayashi, Etsuro ItoAdachi, Yasuhiko Ikeda, Shotaro Iwamoto, Takashi Taga, Yoshiyuki Kosaka, Seiji Kojima, Yasuhide Hayashi, Etsuro Ito
  • Journal Title: Blood Volume: 116(22) Pages: 4631-4638
  • Peer Reviewed
• [Presentation] GATA1 mutants lacking Rb-binding motif observed in transient abnormal myelopoiesis in Down syndrome (2011)
  • Author(s): Tsutomu Toki
  • Organizer: 53^<rd> American society of hematology annual meeting and exposition
  • Place of Presentation: San Diego Convention Center (San Diego, CA)
  • Year and Date: 2011-12-10
• [Presentation] ダウン症-過性異常骨髄増殖症にみられた新たな内部欠損変異GATA1 (2011)
  • Author(s): 土岐力
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-15
• [Presentation] GATA1 mutants lacking Rb-binding motif observed in transient abnormal myelopoiesis in Down syndrome (2011)
  • Author(s): Tsutomu Toki, Eri Kobayashi, Rika Kanezaki, RuNan Wang, Kiminori Terui , Hirokazu Kanegane, Miho Maeda, Mikiya Endo, Tatsuki Mizuochi, Souichi Adachi, Yasuhide Hayashi, Ritsuko Shimizu, Masayuki Yamamoto, Etsuro Ito
  • Organizer: 第53回米国血液学会
  • Place of Presentation: San Diego Convention Center, California
• [Presentation] Novel GATA1 mutants with internal deletions in transient abnormal myelopoiesis in Down Syndrome (2011)
  • Author(s): Tsutomu Toki, Eri Kobayashi, Rika Kanezaki, Runan Wang, Kiminori Terui, Hirokazu Kanegane, Miho Maeda, Takayoshi Koike, Mikiya Endo, Souichi Adachi, Yasuhide Hayashi, Ritsuko Shimizu, Masayuki Yamamoto, Etsuro Ito
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場
• [Presentation] シンポジウム「TAMにみら れたGATA1遺伝子異常の最近の話題」 (2011)
  • Author(s): 土岐 力
  • Organizer: 第114回日本小児科学会学術集会
  • Place of Presentation: グランドプリンスホテル新高輪
• [Presentation] Internal deletions of transcription factor GATA1 observed in transient abnormal myelopoiesis. (2010)
  • Author(s): Toki T, Kanezaki R, Wang R, Terui K, Hayashi Y, Miura M, Maeda M, Ito E.
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2010-09-26
• [Presentation] シンポジウム「ダウン症候群 と血液腫瘍」 (2009)
  • Author(s): 土岐 力
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2009-10-25
• [Presentation] ダウン症候群と血液腫瘍 (2009)
  • Author(s): 土岐力
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都市
  • Year and Date: 2009-10-25
• [Presentation] Internal deletions of transcription factor GATA1 observed in transient abnormal myelopoiesis (2009)
  • Author(s): Tsutomu Toki, Rika Kanezaki, Ru Nan Wang , Kiminori Terui, Yasuhide Hayashi, Masayoshi Miura, Miho Maeda, Eturo Ito
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシ フィコ横浜