Clinical and biological significance of granulocyte colony stimulating factor receptor gene abnormalities those found in severe congenital neutropenia.

• Project/Area Number: 24591539
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamagata University
• Principal Investigator: Mitsui Tetsuo 山形大学, 医学部, 教授 (30270846)
• Co-Investigator(Kenkyū-buntansha): KAWAKAMI TAKAKO 山形大学, 医学部, 助教 (90312743) ; HAYASAKA KIYOSHI 山形大学, 医学部, 教授 (20142961)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 先天性好中球減少症 / CSF3R / G-CSF受容体 / 切断型遺伝子変異 / 白血病化 / 切断型遺伝子異常 / G-CSF 受容体 / HAX1 / ゲノム不安定性

Outline of Final Research Achievements

We conducted sequential granulocyte colony stimulating factor (CSF3) receptor gene analysis of patients with severe congenital neutropenia. No mutation was found in CSF3R gene during study period. Some genes for proteins of signal transduction of CSF3R were also analyzed and also found no abnormality. During study period no patient progressed to myelodysplasia or myeloid leukemia.
Prospective analysis toward severe congenital neutropenia is seemed to be difficult. It is rare disease and the patients tend to receive blood cell transplant in their clinical course before progression to leukemia. New approach should be arranged to define the mechanism of leukemogenesis of this disease.

Research Products

• [Journal Article] Allogeneic hematopoietic stem cell transplantation for Chediak-Higashi syndrome. (2016)
  • Author(s): Umeda K, Adachi S, Horikoshi Y, Imai K, Terui K, Endo M, Mitsui T, Kato K, Koh K, Kajiwara R, Ito R, Otsuka Y, Inoue M, Ishii E, Yabe H.
  • Journal Title: Pediatiric Transplant Volume: 20 Issue: 2 Pages: 271-5
  • DOI: 10.1111/petr.12626
  • Peer Reviewed
• [Journal Article] Gene alterations involving the CRLF2-JAK pathway and recurrent gene deletions in Down syndrome-associated acute lymphoblastic leukemia in Japan. (2014)
  • Author(s): Hanada I, Terui K, Ikeda F, Toki T, Kanezaki R, Sato T, Kamio T, Kudo K, Sasaki S, Takahashi Y, Hayashi Y, Inukai T, Kojima S, Koike K, Kosaka Y, Kobayashi M, Imaizumi M, Mitsui T, Hori H, Hara J, Horibe K, Nagai J, Goto H, Ito E.
  • Journal Title: Genes Chromosomes Cancer Volume: 53 Issue: 11 Pages: 902-910
  • DOI: 10.1002/gcc.22201
  • Peer Reviewed / Open Access
• [Journal Article] Identification of Novel ALK Rearrangement A2M-ALK in a Neonate with Fetal Lung Interstitial Tumor (2014)
  • Author(s): Onoda T, Kanno M, Sato H, Takahashi N, Izumino H, Ohta H, Emura T, Katoh H, Ohizumi H, Ohtake H, Asao H, Dehner LP, Hill AD, Hayasaka K, Mitsui T
  • Journal Title: Genes Chromosomes Cancer Volume: 53 Issue: 10 Pages: 865-874
  • DOI: 10.1002/gcc.22199
  • Peer Reviewed
• [Journal Article] Improved Treatment Results of Children With B-Cell Non-Hodgkin Lymphoma: A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group B-NHL03 Study (2014)
  • Author(s): Tsurusawa M, Mori T, Kikuchi A, Mitsui T, Sunami S, Kobayashi R,Takimoto T, Saito A,Watanabe T,Fujimoto J, Nakazawa A, Ohshima K and Horibe K
  • Journal Title: Pediat Blood Cancer Volume: 61 Issue: 7 Pages: 1215-1221
  • DOI: 10.1002/pbc.24975
  • Peer Reviewed
• [Journal Article] Successful treatment of acute myeloid leukaemia in a patient with ataxia telangiectasia. (2013)
  • Author(s): Tadashi Onoda, Miyako Kanno, Toru Meguro, Hiroko Sato, Noriyuki Takahashi, Takako Kawakami, Tetsuo Mitsui, Kiyoshi Hayasakai
  • Journal Title: Europ J Haematol Volume: 91 Issue: 6 Pages: 557-560
  • DOI: 10.1111/ejh.12186
  • Peer Reviewed
• [Journal Article] Stem cell transplantation for paediatric patients with non-anaplastic peripheral T-cell lymphoma in Japan. (2012)
  • Author(s): R Kobayashi,N Fujita,T Mitsui,F Iwasaki,J Suzumiya,H Kuroda,R Nishimura,Y Sasahara,Y Takeshita,K Kato, H Okumura, H Sakamaki,H Yabe,K Kawa, K Kato and R Suzuki
  • Journal Title: British Journal of Haematology Volume: 159 Issue: 1 Pages: 88-93
  • DOI: 10.1111/bjh.12001
  • Peer Reviewed
• [Presentation] PRF1遺伝子領域の片親性ダイソミーが原因であった家族性血球貪食症候群の2か月女児 (2015)
  • Author(s): 佐藤裕子、川崎直未、川崎基、安孫子優、目黒亨、高橋憲幸、簡野美弥子、滝智彦、今村俊彦、三井哲夫
  • Organizer: 日本小児血液・がん学会学術集会
  • Place of Presentation: 甲府富士屋ホテル（山梨県甲府市）
  • Year and Date: 2015-11-27
• [Presentation] 小児がん治療後の口腔内がん3例 (2014)
  • Author(s): 三井 哲夫, 川上 貴子, 簡野 美弥子, 高橋 憲幸, 小野田 正志, 目黒 亨, 佐藤 裕子, 早坂 清
  • Organizer: 日本小児血液がん学会
  • Place of Presentation: 岡山コンベンションセンター 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] ALK 2p23転座と新規融合遺伝子A2M-ALKを同定したFetal Lung Interstitial Tumor (2014)
  • Author(s): 小野田 正志, 簡野 美弥子, 佐藤 裕子, 高橋 憲幸, 五十野 博子, 太田 寛, 江村 隆起, 大竹 浩也, Hill Ashley D., 早坂 清, 三井 哲夫
  • Organizer: 日本小児血液がん学会
  • Place of Presentation: 岡山コンベンションセンター 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Kasabach-Merritt現象を伴い難治性であった巨大血管腫に対し3剤併用療法を行い保存的に治療し得た生後1ヵ月女児 (2014)
  • Author(s): 目黒 亨, 簡野 美弥子, 高橋 憲幸, 上村 雄太, 小野田 正志, 佐藤 裕子, 三井 哲夫
  • Organizer: 日本小児血液がん学会
  • Place of Presentation: 岡山コンベンションセンター 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Stem cell transplantation for anaplastic large cell lymphoma of children and adolescent in Japan
  • Author(s): Reiji Fukano，Ryoji Kobayashi，Tetsuo Mitsui，Naoto Fujita，Fuminori Iwasaki，Junji Suzumiya，Mikiya Endo，Hisato Kigasawa，Hideo Mugishima，Akira Hayakawa，Jiro Inagaki，Hisashi Sakamaki，Souichi Adachi，Keisei Kawa，Koji Kato，Ritsuro Suzuki.
  • Organizer: 第75回日本血液学会学術集会
  • Place of Presentation: 札幌市、ロイトン札幌
• [Presentation] 重症好中球減少症の経過中、5歳時急性脳症を契機に退行を認め神経発達障害が顕在化したHAX1を有する女児
  • Author(s): 目黒亨、中村和幸、佐藤裕子、簡野美弥子、高橋憲幸、小野田正志、川上貴子、三井哲夫、加藤光広、早坂清
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡市、ヒルトン福岡シーホーク
• [Presentation] 2013年山形県南部で発症した甲状腺がん18歳男児の1例
  • Author(s): 本間信夫、橋本敏夫、角田力彌、三井哲夫、早坂清
  • Organizer: 第55回日本小児血液・がん学会学術集会
  • Place of Presentation: 福岡市、ヒルトン福岡シーホーク