Comprehensive analysis of splicing variants characteristic of acute myelogenous leukemia stem cells

2011 Fiscal Year Final Research Report

• Project/Area Number: 21790334
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Nagoya City University (2010-2011); The Institute of Physical and Chemical Research (2009)
• Principal Investigator: KITAMURA Hiroshi 名古屋市立大学, 大学院・医学研究科, 准教授 (80312403)
• Co-Investigator(Renkei-kenkyūsha): OHARA Osamu 独立行政法人理化学研究所, 免疫アレルギー科学総合研究センター, グループディレクター (20370926) ; ISHIKAWA Fumihiko 独立行政法人理化学研究所, 免疫アレルギー科学総合研究センター, グループディレクター (30403918)
• Project Period (FY): 2009 – 2011
• Keywords: マイクロアレイ / ゲノム / 骨髄性白血病 / 白血病幹細胞 / トランスクリプトーム / スプライシング / エクソンアレイ

Research Abstract

In this study, we attempted to identify genes whose exon usage is modulated in acute myelogenous leukemia(AML) stem cells. Taking advantage of Affymetrix Exon 1.0ST arrays, we evinced that 117 genes represent distinct exon usage compared with hematopoietic stem cells from healthy volunteers. In addition, total 481 transcripts showed expressional changes in AML stem cells. We also found 16 genes undergo changes in exon usage along with differentiation of AML-like cell lines. Although we failed to find genes responsible for leukemogenesis in gene transfer studies, some genes/splicing variants regulates inflammatory responses.

Research Products

• [Journal Article] (2011)
  • Author(s): Masatoshi Ito, Hiroshi Kitamura, Chisato Kikuguchi, Koji Hase, Hiroshi Ohno, and Osamu Ohara
  • Journal Title: Cell Struct. Funct. Volume: 36(1) Pages: 27-33
  • DOI: DOI:10.1247/csf.10025
  • Peer Reviewed
• [Journal Article] The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4^+T cells (2011)
  • Author(s): Yasutaka Motomura, Hiroshi Kitamura, Atsushi Hijikata, Yuko Matsunaga, Koichiro Matsumoto, Horomasa Inoue, Koji Atarashi, Shohei Hori, Hiroshi Watarai, Jinfang Zhu, Masaru Taniguchi, Masato Kubo
  • Journal Title: Nat. Immunol Volume: 12(5) Pages: 450-459
  • DOI: DOI:10.1038/ni.2020
  • Peer Reviewed
• [Journal Article] CCR6hiCD11cint B cells promote M-cell differentiation in Peyer's patch (2011)
  • Author(s): Masashi Ebisawa, Koji Hase, Daisuke Takahashi1, Hiroshi Kitamura, Kathryn A. Knoop, Ifor R. Williams, Hiroshi Ohno
  • Journal Title: Int. Immunol Volume: 23(4) Pages: 261-269
  • DOI: DOI:10.1093/intimm/dxq478
  • Peer Reviewed
• [Journal Article] Mammalian polycomb-like Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate polycomb activity both at the Hox gene cluster and at Cdkn2a genes (2011)
  • Author(s): Xiangzhi Li, Kyo-ichi Isono, Daisuke Yamada, Takaho A. Endo, Mitsuhiro Endoh, Jun Shinga, Yoko Mizutani-Koseki, Arie P. Otte, Miguel Casanova, Hiroshi Kitamura, Takehiko Kamijo, Jafar Sharif, Osamu Ohara, Tetsuro Toyada, Bradley E. Bernstein, Neil Brockdorff, and Haruhiko Koseki
  • Journal Title: Mol. Cell. Biol Volume: 31(2) Pages: 351-364
  • DOI: DOI:10.1128/MCB.00259-10
  • Peer Reviewed
• [Journal Article] Characterization of multiple alternative forms of heterogeneous nuclear ribonucleoprotein K by phosphate-affinity electrophoresis (2010)
  • Author(s): Yayoi Kimura, Kayoko Nagata, Nobutake Suzuki, Ryo Yokoyama, Yuko Yamanaka, Hiroshi Kitamura, Hisashi Hirano, Osamu Ohara
  • Journal Title: Proteomics Volume: 10(21) Pages: 3884-3895
  • DOI: DOI:10.1002/pmic.201000349
  • Peer Reviewed
• [Journal Article] A set of gene associated with the interferone-response and survival of lung cancer patients undergoing alpha-galactosylceramide-pulsed dendritic cell therapy (2010)
  • Author(s): Kosuke Okita, Shinichiro Motohashi, Ryo Shinnakasu, Kaoru, Nagato, Kazuki Yamasaki, Yasunori Sato, Hiroshi Kitamura, Atsushi Hijikata, Masakatsu Yamashita, Kanako Shimizu, Shin-ichiro Fujii, Osamu Ohara, Masaru Taniguchi, Isao Sakaida, Toshinori Nakayama.
  • Journal Title: Cancer Sci. Volume: 101(11) Pages: 2333-2340
  • DOI: DOI:10.1111/j.1349-7006.2010.01696.x
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): Yoriko Saito*, Hiroshi Kitamura*, Atsushi Hijikata, Mariko Tomizawa-Murasawa, Satoshi Tanaka, Shinsuke Takagi, Naoyuki Uchida, Nahoko Suzuki, Akiko Sone, Yuho Najima, Hidetoshi Ozawa, Atsushi Wake, Shuichi Taniguchi, Leonard D Shultz, Osamu Ohara, Fumihiko Ishikawa
  • Journal Title: Sci. Transl. Med. Volume: 2(17) Pages: 17-9
  • DOI: DOI:10.1126/scitranslmed.3000349
  • Peer Reviewed
• [Journal Article] The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut (2010)
  • Author(s): Keiichiro Suzuki, Mikako Maruya, Shimpei Kawamoto, Katarzyna Sitnik, Hiroshi Kitamura, William W. Agace, Sidnia Fagarasan
  • Journal Title: Immunity Volume: 33(1) Pages: 71-83
  • DOI: DOI:10.1016/j.immuni.2010.07.003
  • Peer Reviewed
• [Journal Article] M-Sec promotes membrane nanotube formation by interacting with Ral and the exocyst complex (2009)
  • Author(s): Koji Hase, Shunsuke Kimura, Hiroyuki Takatsu, Masumi Ohmae, Sayaka Kawano, Hiroshi Kitamura, Masatoshi Ito, Hiroshi Watarai, C. Clayton Hazelett, Charles Yeaman, Hiroshi Ohno
  • Journal Title: Nat. CellBiol Volume: 11(12) Pages: 1427-1432
  • DOI: DOI:10.1038/ncb1990
  • Peer Reviewed
• [Journal Article] Deficiency of the oxidative damage-specific DNA glycosylase NAIL1 leads to reduced germinal center B cell expansion (2009)
  • Author(s): Hiromi Mori, Rika Ouchida, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Yingqian Li, Xiang Gao, Akira Yasui, R. Stephan Lloyd, Ji-Yang Wang
  • Journal Title: DNA Repair(Amst) Volume: 8(11) Pages: 1328-1332
  • DOI: DOI:10.1016/j.dnarep.2009.08.007
  • Peer Reviewed
• [Journal Article] Mina an Il4 repressor, controls T helper type 2 bias (2009)
  • Author(s): Mariko Okamoto, Melanie Van Stry, Linda Chung, Madoka Koyanagi, Xizhang Sun, Yoshie Suzuki, Osamu Ohara, Hiroshi Kitamura, Atsushi Hijikata, Masato Kubo, Mark Bix
  • Journal Title: Nat. Immunol. Volume: 10(8) Pages: 872-879
  • DOI: DOI:10.1038/ni.1747
  • Peer Reviewed
• [Journal Article] Dentification of a novel subset of CD8+dendritic cells responsible for tolerance induction of cell-associated antigens (2009)
  • Author(s): Chun-Hong Qin, Yasunobu Miyake, Hitomi Kaise, Hiroshi Kitamura, Osamu Ohara, Masato Tanaka
  • Journal Title: J. Immunol. Volume: 182(7) Pages: 4127-4136
  • DOI: DOI:10.4049/jimmunol.0803364
  • Peer Reviewed
• [Journal Article] Naturally occurring regulatory dendritic cells regulate murine cutaneous graft-versus-host disease (2009)
  • Author(s): Kaori Sato, Kawori Eizumi, Tomohiro Fukaya, Shigeharu Fujita, Yumiko Sato, Hideaki Takagi, Mai Yamamoto, Naohide Yamashita, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Sho Yamasaki, Takashi Saito, Katsuaki Sato
  • Journal Title: Blood Volume: 113(19) Pages: 4780-4789
  • DOI: DOI:10.1182/blood-2008-10-183145
  • Peer Reviewed
• [Presentation] マクロファージの新たな機能制御分子による2型糖尿病関連分子の発現調節 (2011)
  • Author(s): 北村浩、伊藤誠敏、木村俊介、嶋本良則、小林敦夫、菊口千智、岡部潤、渡会浩志、小原收、三好一郎
  • Organizer: 第152回日本獣医学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 20110919-21
• [Presentation] モダンゲノミクスの成果と展望-如何に使いこなすか?- (2011)
  • Author(s): 北村浩
  • Organizer: 東海実験動物研究会2011年例会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-07-23
• [Remarks]
  • URL: http://www.med.nagoya-cu.ac.jp/animal.dir/animalweb/dcem/index_ncu.html
• [Remarks]
  • URL: http://www.facebook.com/dcemncu
• [Patent(Industrial Property Rights)] Leukemia Stem Cell Markers (2011)
  • Inventor(s): 石川文彦、小原收、齊藤頼子、北村浩、土方敦司、小澤秀俊
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: 特許、JP2010055131
  • Acquisition Date: 2011-04-11
  • Overseas