Isolation of novel anti-oncogenes using transposon in model mice for chronic myelogenous leukemia

• Project/Area Number: 20591126
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: HONDA Hiroaki Hiroshima University, 原爆放射線医科学研究所, 教授 (40245064)
• Co-Investigator(Kenkyū-buntansha): HONDA ZenーIchiro 東京大学, 医学部附属病院, 講師 (70238814) ; HORIE Kyoji 大阪大学, 医学(系)研究科, 准教授 (30333446)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 慢性骨髄性白血病 / トランスポゾン / がん抑制遺伝子

Research Abstract

Chronic mylogeous leukemia (CML) is a disorder of hematopoietic stem cells, and is characterized in that after several years' duration of chronic phase, it inevitably accelerates and progresses into fatal blast phase resembling to acute leukemia (blast crisis). Blast crisis is considered to be caused by loss of anti-oncogene (s), but its precise mechanism (s) remains unclear. To isolate novel anti-oncogene (s), we crossed CML transgenic mice with transposon transgenic mice, transposase knockin mice, and Bloom suppression mice. Mice with aimed genetic background were obtained and currently their phenotypes were being analyzed.

Research Products

• [Journal Article] Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation. (2011)
  • Author(s): Honda H, Takubo K, Oda H, Kosaki K, Tazaki T, Yamasaki N, Miyazaki K, Moore KA, Honda ZI, Suda T, Lemischka IR.
  • Journal Title: Proc Natl Acad Sci USA 108(6) Pages: 2468-2473
• [Journal Article] Hemp, an mbt domain-containing protein, plays essential roles in hematopoietic stem cell function and skeletal formation. (2011)
  • Author(s): Honda H, Takubo K, Oda H, Kosaki K, Tazaki T, Yamasaki N, Miyazaki K, Moore KA, Honda Zi, Suda T, Lemischka IR.
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Pages: 2468-2473
  • Peer Reviewed
• [Journal Article] The role of the basic helix-loop-helix transcription factor Dec1 in the regulatory T cells. (2010)
  • Author(s): Miyazaki K, Miyazaki M, Guo Y, Yamasaki N, Kanno M, Honda Zi, Oda H, Kawamoto H, Honda H.
  • Journal Title: J Immunol 385(12) Pages: 7330-7339
• [Journal Article] A 5' untranslated region containing the IRES element in the Runx1 gene is required for angiogenesis, hematopoiesis and leukemogenesis in a knock-in mouse model. (2010)
  • Author(s): Nagamachi A, Htun PW, Ma F, Miyazaki K, Yamasaki N, Kanno M, Inaba T, Honda Zi, Okuda T, Oda H, Tsuji K, Honda H.
  • Journal Title: Dev Biol 345 Pages: 226-236
• [Journal Article] p130Cas plays essential roles in liver development by regulating sinusoidal endothelial cell fenestration. (2010)
  • Author(s): Tazaki T, Sasaki T, Uto K, Yamasaki N, Tashiro S, Sakai R, Tanaka M, Oda H, Honda Zi, Honda H.
  • Journal Title: Hepatology 52 Pages: 1089-1099
• [Journal Article] Identification of Zfp521/ZNF521 as a cooperative gene for E2A-HLF to develop acute B-lineage leukemia. (2010)
  • Author(s): Yamasaki N, Miyazaki K, Nagamachi A, Koller R, Oda H, Miyazaki M, Sasaki T, Honda Zi, Wolff L, Inaba T, Honda H.
  • Journal Title: Oncogene 29 Pages: 1963-1975
• [Journal Article] Identification of Zfp521/ZNF521 as a cooperative gene for E2A-HLF to develop acute B-lineage leukemia. (2010)
  • Author(s): Yamasaki N, Miyazaki K, Nagamachi A, Koller R, Oda H, Miyazaki M, Sasaki T, Honda Zi, Wolff L, Inaba T, Honda H.
  • Journal Title: Oncogene Volume: 29 Pages: 1963-1975
  • Peer Reviewed
• [Journal Article] pl30Cas plays essential roles in liver development by regulating sinusoidal endothelial cell fenestration. (2010)
  • Author(s): Tazaki T, Sasaki, Uto K, Yamasaki N, Tashiro S, Sakai R, Tanaka M, Oda H, HondaZi, Honda H.
  • Journal Title: Hepatology Volume: 52 Pages: 1089-1099
  • Peer Reviewed
• [Journal Article] A 5' untranslated region containing the IRES element in the Runx1 gene is required for angiogenesis, hematopoiesis and leukemogenesis in a knock-in mouse model. (2010)
  • Author(s): Nagamachi A, Htun P W, Ma F, Miyazaki K, Yamasaki N, Kanno M, Inaba T, Honda Zi, Okuda T, Oda H, Tsuji K, Honda H.
  • Journal Title: Developmental Biology Volume: 345 Pages: 226-236
  • Peer Reviewed
• [Journal Article] The role of the basic helix-loop-helix transcription factor Dec1 in the regulatory T cells. (2010)
  • Author(s): Miyazaki K, Miyazaki M, Guo Y, Yamasaki N, Kanno M, Honda Zi, Oda H, Kawamoto H, Honda H.
  • Journal Title: Journal of Immunology Volume: 385 Pages: 7330-7339
  • Peer Reviewed
• [Journal Article] Identification of CENP-V as a novel microtubule-associating molecule that activates Src family kinases through SH3 domain interaction. (2009)
  • Author(s): Honda Zi, Suzuki T, Honda H.
  • Journal Title: Genes Cells 14 Pages: 1383-1394
• [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. (2009)
  • Author(s): Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S.
  • Journal Title: Nature 460 Pages: 904-908
• [Journal Article] Haploinsufficiency and acquired loss of Bcl11b and H2AX induced blast crisis of chronic myelogenous leukemia in a transgenic mouse model. (2009)
  • Author(s): Nagamachi A, Yamasaki N, Miyazaki K, Oda H, Miyazaki M, Honda Zi, Kominami R, Inaba T, Honda H.
  • Journal Title: Cancer Sci 100 Pages: 1219-1226
  • NAID: 10027191952
• [Journal Article] Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia. (2009)
  • Author(s): Miyazaki K, Yamasaki N, Oda H, Kuwata T, Kanno Y, Miyazaki M, Komeno Y, Kitaura J, Honda Zi, Warming S, Jenkins NA, Copeland NG, Kitamura T, Nakamura T, Honda H.
  • Journal Title: Blood 113 Pages: 4702-4710
• [Journal Article] Elevated intraocular pressure, optic nerve atrophy, and impaired retinal development in ODAG transgenic mice. (2009)
  • Author(s): Sasaki T, Watanabe W, Muranishi Y, Kanamoto T, Aihara M, Miyazaki K, Tamura H, Saeki T, Oda H, Souchelnytskyi N, Souchelnytskyi S, Hirohiko A, Honda Zi, Furukawa T, Mishima HK, Kiuchi Y, Honda H.
  • Journal Title: Invest Ophthalmol Vis Sci 50 Pages: 242-248
• [Journal Article] Enhanced expression of p210BCR/ABL and aberrant expression of Zfp423/ZNF423 induce blast crisis of chronic myelogenous leukemia. (2009)
  • Author(s): Miyazaki K, 13名, Honda H.
  • Journal Title: Blood 27 Pages: 4702-4710
  • Peer Reviewed
• [Journal Article] Haploinsufficiency and acquired loss of Bcl11b and H2AX induced blast crisis of chronic myelogenous leukemia in a transgenic mouse model. (2009)
  • Author(s): Nagamachi A, 7名, Honda H.
  • Journal Title: Cancer Sci. 100 Pages: 1219-1226
  • NAID: 10027191952
  • Peer Reviewed
• [Journal Article] Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. (2009)
  • Author(s): Sanada M, 6名, Honda H, 20名, Ogawa S.
  • Journal Title: Nature 100 Pages: 904-908
  • Peer Reviewed
• [Journal Article] Overexpression of ocular development-associated gene (ODAG) in the eye induced elevated intraocular pressure, optic nerve atrophy, and impaired retinal development. (2009)
  • Author(s): Sasaki T, Watanabe W, Muranishi Y, Kanamoto T, Aihara M, Miyazaki K, Tamura H, Saeki T, Oda H, Souchelnytskyi N, Souchelnytskyi S, Hirohiko A, Honda Z-i, Furukawa T, Mishima HK, Kiuchi Y, Honda H
  • Journal Title: Invest Ophthalmol Vis Sci. 50 Pages: 242-248
  • Peer Reviewed
• [Journal Article] Overexpression/enhanced kinase activity of BCR/ABL and altered expression of Notch1 induced acute leukemia in p210BCR/ABL transgenic mice. (2008)
  • Author(s): Mizuno T, Yamasaki N, Miyazaki K, Tazaki T, Koller R, Oda H, Honda Zi, Ochi M, Wolff L, Honda H.
  • Journal Title: Oncogene 27 Pages: 3465-3474
  • NAID: 120001192643
• [Journal Article] Functional analysis of Src homology 3-encoding exon (exon 2) of p130Cas in primary fibroblasts derived from exon 2-specific knockout mice. (2008)
  • Author(s): Tazaki T, Miyazaki K, Hiyama E, Nakamoto T, Sakai R, Yamasaki N, Honda Zi, Noda M, Miyasaka N, Sueda T, Honda H.
  • Journal Title: Genes Cells 13 Pages: 145-157
• [Journal Article] Pre-TCR-induced thymocyte proliferation is epigenetically maintained through BMI-1-mediated p19Arf repression. (2008)
  • Author(s): Miyazaki M, Miyazaki K, Itoi M, Katoh Y, Guo Y, Kanno R, Katoh-Fukui Y, Honda H, Amagai T, van Lohuizen M, Kawamoto H, Kanno M.
  • Journal Title: Immunity 28 Pages: 231-245
• [Journal Article] Overexpression/enhanced kinase activity of BCR/ABL and altered expression of Notchl induced acute leukemia in p210BCR/ABL transgenic mice. (2008)
  • Author(s): Mizuno T, Yamasaki N, Miyazaki K, Tazaki T, Koller R, Oda H, Honda Z-i, Ochi M, Wolff L, Honda H.
  • Journal Title: Oncogene 27 Pages: 3465-3474
  • Peer Reviewed
• [Presentation] Deregulated expression of Fbxl10, a histone demethylase, contributes to leukemia development. (2010)
  • Author(s): Ueda T, Inagaki M, Nagamachi A, Yamasaki N, Matsui H, Takubo K, Konuma T, Suda T, Iwama A, Inaba T, Honda H
  • Organizer: 第72回日本血液学会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-25
• [Presentation] 造血細胞におけるWnt5aの欠失はp210BCR/ABLによって引き起こされるCMLを増悪させる (2010)
  • Author(s): 稲垣舞子、小山浩史、菊池章、本田浩章
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] Unique Gain-of-Function of Mutated c-CBL Tumor Suppresor in Myeloid Neoplasms. (2009)
  • Author(s): Sanada M, 5名 本田浩章, 14名, Ogawa S.
  • Organizer: 51th Annual Meeting of American Society of Hematology
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2009-12-05
• [Presentation] ヒストン脱メチル化酵素Fbxl10の7q- AML/MDS発症過程への関与 (2009)
  • Author(s): 長町安希子, 8名, 本田浩章
  • Organizer: 日本血液学会年会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-24
• [Presentation] bHLH型転写因子Declの発現調節はT細胞の胸腺内セレクションと分化に必要である (2008)
  • Author(s): 宮崎和子, 宮崎正輝, 山崎憲政, 菅野雅元, 本田浩章
  • Organizer: 日本血液学会年会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-12
• [Presentation] bHLH型転写因子Dec1の発現調節はT 細胞の胸腺内セレクションと分化に必要である (2008)
  • Author(s): 宮崎和子, 宮崎正輝, 山崎憲政, 菅野雅元, 本田浩章
  • Organizer: 日本血液学会年会
  • Place of Presentation: 京都
  • Year and Date: 2008-10-10
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