Isolation and characterization of genes involved in the abnormalities of mitosis and nuclear morphology found in myelodysplastic syndromes.

• Project/Area Number: 22659181
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: Hiroshima University
• Principal Investigator: INABA Toshiya 広島大学, 原爆放射線医科学研究所, 教授 (60281292)
• Co-Investigator(Kenkyū-buntansha): MATSUI Hirotaka 広島大学, 原爆放射線医科学研究所, 准教授 (60379849)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,140,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: MDS / エピゲノム制御 / 骨髄異形成症候群 / 7番染色体欠損 / 発がん抑制遺伝子 / 遺伝子欠損マウス / エンドソーム代謝 / 骨髄性白血病 / 分裂期異常

Research Abstract

The aim of this study is isolation and characterization of genes involved in the abnormalities of mitosis and nuclear morphology frequently found in myelodysplastic syndromes(MDS). We identified Miki and CG-NAP as crucial members of the transportation system for pericentriolar materials(Mol. Cell), and dynactin-3 that maintains centrosome function in the metaphase(JBC).

Research Products

• [Journal Article] (2012) A modified system for analyzing ionizing radiation-induced chromosome abnormalities (2012)
  • Author(s): Shi, L., Fujioka, K., Sun, J., Kinomura, A., Inaba, T., Ikura, T., Ohtaki, M., Yoshida, M., Kodama, Y., Livingston, G. K., Kamiya, K., and Tashiro, S
  • Journal Title: Radiat Res Volume: 177 Pages: 533-538
• [Journal Article] (2011) Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma (2011)
  • Author(s): Jin, L., Tabe, Y., Kimura, S., Zhou, Y., Kuroda, J., Asou, H., Inaba, T., Konopleva, M., Andreeff, M., and Miida, T.
  • Journal Title: Br. J. Cancer Volume: 104 Pages: 91-100
  • Peer Reviewed
• [Journal Article] (2011) The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase (2011)
  • Author(s): Ozaki, Y., Matsui, H., Nagamachi, A., Asou, H., Aki, D., and Inaba, T.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 5589-5598
  • Peer Reviewed
• [Journal Article] (2011) TheSamd9L Gene : Transcriptional Regulation and Tissue-Specific Expression in Mouse Development (2011)
  • Author(s): Jiang, Q., Quaynor, B., Sun, A., Li, Q., Matsui, H., Honda, H., Inaba, T., Sprecher, E., ans Uitto, J.
  • Journal Title: J Invest Dermatol Volume: 131 Pages: 1428-1434
  • Peer Reviewed
• [Journal Article] (2011) Rapid emergence of telaprevir resistant hepatitis C virus strain from wildtype clone in vivo. (2011)
  • Author(s): Hiraga, N., Imamura, M., Abe, H., Hayes, C. N., Kono, T., Onishi, M., Tsuge, M., Takahashi, S., Ochi, H., Iwao, E., Kamiya, N., Yamada, I., Tateno, C., Yoshizato, K., Matsui, H., Kanai, A., Inaba, T., Tanaka, S., and Chayama, K.
  • Journal Title: Hepatology Volume: 54 Pages: 781-788
  • Peer Reviewed
• [Journal Article] (2011) Cas-L regulates myeloid cell motility and suppresses progression of leukemia induced by p210Bcr/ Abl (2011)
  • Author(s): Seo, S., Nakamoto, T., Takeshita, M., Lu, J., Sato, T., Suzuki, T., Kamikubo, Y., Ichikawa, M., Noda, M., Ogawa, S., Honda, H., Oda, H. and Kurokawa, M.
  • Journal Title: Cancer Sci Volume: 102 Pages: 2109-2117
• [Journal Article] Rapidemergence of telaprevir resistanthepatitis C virus strain from wildtypeclone in vivo (2011)
  • Author(s): Hiraga N, Imamura M, Abe H, Hayes CN, Kono T, Onishi M, Tsuge M, TakahashiS, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, Matsui H, KanaiA, Inaba T, Tanaka S, Chayama K
  • Journal Title: Hepatology Volume: 54 Issue: 3 Pages: 781-788
  • DOI: 10.1002/hep.24460
  • Peer Reviewed
• [Journal Article] The Samd9L gene : transcriptional regulation and tissue-specific expression in mouse development (2011)
  • Author(s): Jiang Q., et al
  • Journal Title: J Invest Dermatol Volume: 131 Issue: 7 Pages: 1428-1434
  • DOI: 10.1038/jid.2011.61
  • Peer Reviewed
• [Journal Article] Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma (2011)
  • Author(s): Jin L., et al
  • Journal Title: Br.J.Cancer Volume: 104 Pages: 91-100
  • Peer Reviewed
• [Journal Article] The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase (2011)
  • Author(s): Ozaki, Y., et al
  • Journal Title: J.Biol.Chem Volume: 286 Pages: 5589-5598
  • Peer Reviewed
• [Journal Article] Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma. (2011)
  • Author(s): Jin, L., et al
  • Journal Title: Br.J.Cancer Volume: (In press)
  • Peer Reviewed
• [Journal Article] The dynactin complex maintains the integrity of metaphasic centrosomes to ensure transition to anaphase. (2011)
  • Author(s): Ozaki, Y., et al
  • Journal Title: J.Biol.Chem Volume: 286 Pages: 5589-5598
  • Peer Reviewed
• [Journal Article] (2010) Upregulation of survivin by the E2A-HLF chimera is indispensable for the survival of t(17 ; 19)-positive leukemia cells (2010)
  • Author(s): Okuya, M., Kurosawa, H., Kikuchi, J., Furukawa, Y., Matsui, H., Aki, D., Matsunaga, T., Inukai, T., Goto, H., Altura, R. A., Sugita, K., Arisaka, O., Look, A. T., and Inaba, T
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 1850-1860
  • Peer Reviewed
• [Journal Article] (2010) Identification of Zfp521/ ZNF521 as acooperative 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., and Honda, H.
  • Journal Title: Oncogene Volume: 29 Pages: 1963-1975
  • Peer Reviewed
• [Journal Article] (2010) Specific induction of CD33 expression by E2A-HLF : the first evidence for aberrant myeloid antigen expression in ALL by a fusion transcription factor (2010)
  • Author(s): Akahane, K., Inukai, T., Inaba, T., Kurosawa, H., Look, A. T., Kiyokawa, N., Fujimoto, J., Goto, H., Endo, M., Zhang, X., Hirose, K., Kuroda, I., Honna, H., Kagami, J., Goi, K., Nakazawa, S., and Sugita K.
  • Journal Title: Leukemia Volume: 24 Pages: 865-869
  • Peer Reviewed
• [Journal Article] (2010) Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17 ; 19) (2010)
  • Author(s): Hirose, K., Inukai, T., Kikuchi, J., Furukawa, Y., Ikawa, T., Kawamoto, H., Oram, S. H., Gottgens, B., Kiyokawa, N., Miyagawa, Y., Okita, H., Akahane, K., Zhang, X., Kuroda, I., Honna, H., Kagami, K., Goi, K., Kurosawa, H., Look, A. T., Matsui, H., Inaba,
  • Journal Title: Blood Volume: 116 Pages: 962-970
  • Peer Reviewed
• [Journal Article] (2010) A5' 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, Z. I., Okuda, T., Oda, H., Tsuji, K., and Honda, H.
  • Journal Title: Dev. Biol Volume: 345 Pages: 226-236
  • Peer Reviewed
• [Journal Article] Upregulation of survivin by the E2A-HLF chimera is indispensable for the survival of t(17;19)-positive leukemia cells. (2010)
  • Author(s): Okuya, M., et al
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 1850-1860
  • Peer Reviewed
• [Journal Article] Identification of Zfp521/ZNF521 as acooperative gene for E2A-HLF to develop acute B-lineage leukemia. (2010)
  • Author(s): Yamasaki, N., et al
  • Journal Title: Oncogene Volume: 29 Pages: 1963-1975
  • Peer Reviewed
• [Journal Article] Specific induction of CD33 expression by E2A-HLF : the first evidence for aberrant myeloid antigen expression in ALL by a fusion transcription factor. (2010)
  • Author(s): Akahane, K., et al
  • Journal Title: Leukemia Volume: 24 Pages: 865-869
  • Peer Reviewed
• [Journal Article] Aberrant induction of LMO2 by the E2A-HLF chimeric transcription factor and its implication in leukemogenesis of B-precursor ALL with t(17;19). (2010)
  • Author(s): Hirose, K., et al
  • Journal Title: Blood Volume: 116 Pages: 962-970
  • 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., et al
  • Journal Title: Dev Biol. Volume: 345 Pages: 226-236
  • Peer Reviewed
• [Journal Article] Oncogenic Fusion E2A-HLF Sensitizes t(17 ; 19)-positive Acute Lymphoblastic Leukemia toTRAIL-Mediated Apoptosis by Upregulating the Expression of Death Receptors
  • Author(s): Zhang, X., Inukai, T., Hirose, K., Akahane, K., Kuroda, I., Honna-Oshiro, H., Kagami, K., Goi, K., Nakamura, K., Kobayashi, M., Endo, M., Yagita, H., Kurosawa, H., Look, A. T., Honda, H., Inaba, T., Nakazawa, S., and Sugita, K.
  • Journal Title: Leukemia Volume: in press
• [Journal Article] Mouse Samd9l is not a functional paralogue of the human SAMD9, the gene mutated in normophosphataemic familial tumoral calcinosis
  • Author(s): Li, Q., Guo, H., Matsui, H., Honda, H., Inaba, T., Sundberg, J. P., Sprecher, E., and Uitto, J
  • Journal Title: Exp. Dermatol Volume: in press
• [Journal Article] EED mutants impair polycomb repressive complex 2 in myelodysplastic syndrome and related neoplasms
  • Author(s): Ueda, T., Sanada, M., Matsui, H., Yamasaki, N., Honda, Zi., Shih, L. Y., Mori, H., Inaba, T., Ogawa, S.
  • Journal Title: Leukemia Volume: in press
• [Journal Article] Poly-ADP ribosylation of Miki by tankyrase-1 promotes centrosome maturation
  • Author(s): Ozaki, Y., Matsui, H., Asou, H., Nagamachi, A., Aki, D., Honda, H., Yasunaga, S., Takihara, Y., Yamamoto, T., Izumi, S., Ohsugi, M., and Inaba, T.
  • Journal Title: Mol. Cell Volume: in press
• [Presentation] a candidate-7/ 7q-responsible gene product, downregulates cytokine signals by facilitating formation of early endosome (2011)
  • Author(s): Matsui, H. Titan(Samd9L)
  • Organizer: 第53回アメリカ血液学会
  • Place of Presentation: サンディエゴ米国
  • Year and Date: 2011-12-12
• [Presentation] Titan (Samd9L), a candidate-7/7q-responsible gene product, downregulates cytokine signals by facilitating formation of early endosome (2011)
  • Author(s): Matsui, H.
  • Organizer: 第53回アメリカ血液学会
  • Place of Presentation: サンディエゴ米国
  • Year and Date: 2011-12-12
• [Presentation] Analysis of epigeneticalterations by 5-Azacitidine that induces erythroid differentiation using a next generation sequencer (2011)
  • Author(s): 松井啓隆
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-15
• [Presentation] Analysis of epigenetic alterations by 5-Azacitidine that induces erythroid differentiation using a next generation sequencer (2011)
  • Author(s): 松井啓隆
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-15
• [Presentation] Analysis of epigenetic changes by 5-Azacitidine that induces erythroid differentiation using a next generation sequencer (2011)
  • Author(s): 松井啓隆
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-05
• [Presentation] Development of myeloid neoplasia in mice deficient for endosome fusion facilitator(eff)-2gene that mimic human-7/ 7q- (2011)
  • Author(s): 松井啓隆
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-05
• [Presentation] Development of myeloid neoplasia in mice deficient for endosome fusion facilitator(eff)-2gene mimic human-7/7q- (2011)
  • Author(s): 松井啓隆
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2011-10-05
• [Presentation] (AstraZeneca, Dept Dev Biol) Titan(Samd9L), a candidate-7/ 7q responsible gene product, downregulates cytokine signals by facilitating formation of early endosomes. (2010)
  • Author(s): Matsui H, Nagamachi A, Ozaki Y, AsouH, Honda H, Inaba T.
  • Organizer: 第52回米国血液学会総会
  • Place of Presentation: 米国オーランド
  • Year and Date: 2010-12-06
• [Presentation] Titan (Samd9L), a candidate -7/7q- responsible gene product, downregulates cytokine signals by facilitating formation of early endosomes. (2010)
  • Author(s): Matsui, H., et al
  • Organizer: 第52回米国血液学会総会
  • Place of Presentation: 米国、オーランド
  • Year and Date: 2010-12-06
• [Presentation] 7番染色体長腕欠損による白血病発症メカニズム:責任遺伝子の単離と機能解析 (2010)
  • Author(s): 松井啓隆
  • Organizer: 第53回放射線影響学会大会(招待講演)
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] (AstraZeneca,疾患モデル解析) Titan(Samd9L), a candidate 7qresponsiblegene product, promotesdegradation of cytokine receptors (2010)
  • Author(s): 松井啓隆, 長町安希子, 尾崎佑子, 麻生博也, 本田浩章, 稲葉俊哉
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Titan (Samd9L), a candidate 7q- responsible gene product, promotes degradation of cytokine receptors. (2010)
  • Author(s): Matsui, H., et al
  • Organizer: 第72回日本血液学会総会
  • Place of Presentation: 横浜市
  • Year and Date: 2010-09-24
• [Presentation] (AstraZeneca,疾患モデル解析) Titan(Samd9L), a candidate 7qresponsiblegene product, promotesdegradation of cytokine receptors (2010)
  • Author(s): 松井啓隆, 長町安希子, 尾崎佑子, 麻生博也, 本田浩章, 稲葉俊哉
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-23
• [Presentation] Titan (Samd9L), a candidate -7/7q- responsible gene product, promotes degradation of cytokine receptors. (2010)
  • Author(s): Matsui, H., et al
  • Organizer: 第69回日本癌学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-09-23
• [Presentation] (La Jolla Inst for Allerg & Immunol, AstraZeneca,疾患モデル解析)稲葉俊哉7q欠失責任遺伝子候補Titanによるサイトカイン受容体分解制御 (2010)
  • Author(s): 松井啓隆, 長町安希子, 尾崎佑子, 安藝大輔, 麻生博也, 本田浩章, 稲葉俊哉
  • Organizer: 第51回原子爆弾後障害研究会
  • Place of Presentation: 長崎
  • Year and Date: 2010-06-06
• [Presentation] (La Jolla Inst for Allerg & Immunol, AstraZeneca,疾患モデル解析,東京女子医大病理) 7q-欠損白血病におけるEvil, Fbxl10の関与 (2010)
  • Author(s): 長町安希子, 松井啓隆, 安藝大輔, 尾崎佑子, 麻生博也, 山崎憲政, 小田秀明, 稲葉俊哉, 本田浩章
  • Organizer: 第51回原子爆弾後障害研究会
  • Place of Presentation: 長崎
  • Year and Date: 2010-06-06
• [Presentation] (La Jolla Inst for Allerg & Immunol)放射線誘発白血病の関連遺伝子Miki/ CG-NAPの分裂期中心体における機能 (2010)
  • Author(s): 尾崎佑子, 松井啓隆, 安藝大輔, 長町安希子, 稲葉俊哉
  • Organizer: 第51回原子爆弾後障害研究会
  • Place of Presentation: 長崎
  • Year and Date: 2010-06-06