Molecular cytogenetic studies on the pathogenesis of feline hematological malignancies and development of pathogenesis-based clinical applications

• Project/Area Number: 18688018
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Clinical veterinary science
• Research Institution: The University of Tokyo
• Principal Investigator: FUJINO Yasuhito The University of Tokyo, 大学院・農学生命科学研究科, 助教 (70401180)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥30,030,000 (Direct Cost: ¥23,100,000、Indirect Cost: ¥6,930,000); Fiscal Year 2008: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2007: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000); Fiscal Year 2006: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
• Keywords: ネコゲノム / リンパ・造血系腫瘍 / 染色体解析 / レトロウイルス / FeLV / 遺伝子再構成 / クローナリティ / CIS / ネコゴノム

Research Abstract

小動物臨床においてしばしば重要な問題となる猫の造血系疾患について、分子細胞遺伝学的手法を用いた病態解析を行い、以下の成果を得た。猫白血病ウイルス(FeLV)感染に伴う造血系腫瘍において、ネコゲノムにおけるFeLV組み込み領域を分子細胞遺伝学的に検出する方法を確立し、新規FeLV共通組み込み領域を発見し腫瘍化との関連性を明らかにするとともに、FeLV関連性腫瘍におけるクローナリティ検出法を開発した。さらに、猫のリンパ腫において新たな細胞免疫学的分類法を確立し、詳細な病型分類、治療指針の策定および予後評価を可能にした。一方、猫免疫不全ウイルス感染症において問題となる血液学的異常を明らかにし、新規抗ウイルス療法の基盤となる方法の開発に成功した。

Research Products

• [Journal Article] Identification of a novel common proviral integration site, flit-1, in feline leukemia virus induced thymic lymphoma (2009)
  • Author(s): Fujino Y, Liao CP, Zhao YS, Pan J, Mathes LE, Hayes KA, Ohno K, Tsujimoto H, Roy-Burman P
  • Journal Title: Virology Mar 30;386(1) Pages: 16-22
• [Journal Article] Prevalence of hematological abnormalities and detection of infected bone marrow cells in asymptomatic cats with feline immunodeficiency virus infection (2009)
  • Author(s): Fujino Y, Horiuchi H, Mizukoshi F, Baba K, Goto-Koshino Y, Ohno K, Tsujimoto H
  • Journal Title: Vet Microbiol. May 12;136(3-4) Pages: 217-25
• [Journal Article] Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein (2009)
  • Author(s): Mizukoshi F, Baba K, Goto Y, Setoguchi A, Fujino Y, Ohno K, Oishi S, Kodera Y, Fujii N, Tsujimoto H
  • Journal Title: Vet Microbiol. Apr 14;136(1-2) Pages: 155-9
• [Journal Article] Inhibitory effect of newly developed CXC-chemokine receptor 4 antagonists on the infection with feline immunodeficiency virus (2009)
  • Author(s): Mizukoshi F, Baba K, Goto-Koshino Y, Setoguchi-Mukai A, Fujino Y, Ohno K, Tamamura H, Oishi S, Fujii N, Tsujimoto H
  • Journal Title: J Vet Med Sci. Jan;71(1) Pages: 121-4
  • NAID: 110007055389
• [Journal Article] Disseminated histiocytic sarcoma with excessive hemophagocytosis in a cat (2009)
  • Author(s): Ide K, Setoguchi-Mukai A, Nakagawa T, Uetsuka K, Nakayama H, Fujino Y, Ohno K, Tsujimoto H
  • Journal Title: J Vet Med Sci. Jun;71(6) Pages: 817-820
  • NAID: 130000134410
• [Journal Article] Identification of a novel common proviral integration site, flit-1, in feline leukemia virus induced thymic lymphoma (2009)
  • Author(s): Fujino Y. et.al.
  • Journal Title: Virology 386 Pages: 18-22
  • Peer Reviewed
• [Journal Article] Prevalence of hematological abnormalities and detection of infected bone marrow cells in asymptomatic cats with feline immunodeficiency virus infection (2009)
  • Author(s): Fuiino Y. et.al.
  • Journal Title: Vet Microbiol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of feline leukemia virusinduced malignancies : insertional mutagenesis (2009)
  • Author(s): Fujino Y. et.al.
  • Journal Title: Vet Immunol Immunopathol 123 Pages: 138-143
  • Peer Reviewed
• [Journal Article] Antiviral activity of membrane fusion inhibitors that target gp40 of the feline immunodeficiency virus envelope protein (2009)
  • Author(s): Mizukoshi F. et.al.
  • Journal Title: Vet Microbiol 136 Pages: 155-159
  • Peer Reviewed
• [Journal Article] Disseminated histiocytic sarcoma with excessive hemophagocytosis in a cat (2009)
  • Author(s): Ide K. et.al.
  • Journal Title: J Vet Med Sci 71(In press)
  • Peer Reviewed
• [Journal Article] Inhibitory effect of newly developed CXCchemokine receptor 4 antagonists on the infection with feline immunodeficiency virus (2009)
  • Author(s): Mizukoshi F. et.al.
  • Journal Title: J Vet Med Sci 71 Pages: 121-124
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of feline leukemia virus-induced malignancies: insertional mutagenesis (2008)
  • Author(s): Fujino Y, Ohno K, Tsujimoto H
  • Journal Title: Vet Immunol Immunopathol. May 15;123(1-2) Pages: 138-43
• [Journal Article] Hypereosinophilic syndrome in two cats (2008)
  • Author(s): Takeuchi Y, Matsuura S, Fujino Y, Nakajima M, Takahashi M, Nakashima K, Sakai Y, Uetsuka K, Ohno K, Nakayama H, Tsujimoto H
  • Journal Title: J Vet Med Sci. Oct;70(10) Pages: 1085-9
  • NAID: 110006967092
• [Journal Article] Inhibition of the replication of feline immunodeficiency virus by lentiviral vector-mediated RNA interference in feline cell lines (2008)
  • Author(s): Baba K, Goto-Koshino Y, Mizukoshi F, Setoguchi-Mukai A, Fujino Y, Ohno K, Tsujimoto H
  • Journal Title: J Vet Med Sci. Aug;70(8) Pages: 777-83
  • NAID: 110006878924
• [Journal Article] Quantitative assessment of minimal residual disease (MRD) in canine lymphoma by using real-time polymerase chain reaction (2008)
  • Author(s): Yamazaki J, Baba K, Goto-Koshino Y, Setoguchi-Mukai A, Fujino Y, Ohno K, Tsujimoto H
  • Journal Title: Vet Immunol Immunopathol. Dec 15;126(3-4) Pages: 321-31
• [Journal Article] Inhibition of the replication of feline immunodeficiency virus by lentiviral vectormediated RNA interference in feline cell lines (2008)
  • Author(s): Baba K. et.al.
  • Journal Title: J Vet Med Sci 70 Pages: 777-783
  • Peer Reviewed
• [Journal Article] Hypereosinophilic syndrome in two cats (2008)
  • Author(s): Takeuchi Y. et.al.
  • Journal Title: J Vet Med Sci 70 Pages: 1085-1089
  • Peer Reviewed
• [Journal Article] Molecular pathogenesis of feline leukemia virus-induced malinanCies: Insertional mutagenesis. (2008)
  • Author(s): Fujino Y., et. al.
  • Journal Title: Vet Immunol Immunopathol. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Application of RNA interference for inhibiting the replication of feline immunodeficiency virus in chronically infected cell lines (2007)
  • Author(s): Baba K, Mizukoshi F, Goto-Koshino Y, Setoguchi-Mukai A, Fujino Y, Ohno K, Tsujimoto H
  • Journal Title: Vet Microbiol. Mar 10;120(3-4) Pages: 207-16
• [Journal Article] Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene (2007)
  • Author(s): Matsuura S, Koto H, Ide K, Fujino Y, Setoguchi-Mukai A, Ohno K, Tsujimoto H
  • Journal Title: Am J Vet Res. Jan;68(1) Pages: 95-100
• [Journal Article] Application of RNA interference for inhibiting the replication of feline immunodeficiency virus in chronically infected cell lines. (2007)
  • Author(s): Baba K
  • Journal Title: Veterinary Microbiology 120(3-4) Pages: 207-216
• [Journal Article] Induction of chemoresistance in a cultured canine cell line by retroviral transduction of the canine multidrug resistance 1 gene. (2007)
  • Author(s): Matsuura S
  • Journal Title: American Journal of Veterinary Research 68(1) Pages: 95-100
• [Journal Article] Essential thrombocythemia in a dog (2006)
  • Author(s): Mizukoshi T, Fujino Y, Yasukawa K, Matumoto H, Matsumura S, Nagasaki T, Ohno K, Tsujimoto H, Shimoda T
  • Journal Title: J Vet Med Sci. Nov;68(11) Pages: 1203-6
  • NAID: 130000448046
• [Journal Article] Essential thrombocythemia in a dog. (2006)
  • Author(s): Mizukoshi T
  • Journal Title: Journal of Veterinary Medical Science 68(11) Pages: 1203-1206
• [Journal Article] Assignment of the feline pim-1 and fit-1, common integration sites of feline leukemia virus, to chromosome B2 q21.3 and q32
  • Author(s): Fujino Y, Nishigaki K, Cho KW, Ohno K, Satoh H, Tsujimoto H.
  • Journal Title: Cytogenet Genome Res. (Submitted)
• [Journal Article] Chromosomal mapping of feline leukemia virus insertions in cat lymphoid tumors
  • Author(s): Fujino Y, Satoh H, Ohno K, Tsujimoto H
  • Journal Title: J Virol Methods (Submitted)
• [Journal Article] Cytomorphological and immunological classification of feline lymphomas: a clinical study of 76 cases
  • Author(s): Chino J, Fujino Y, Yamazaki J, Takeuchi Y, Goto-Koshino Y, Nakashima K, Sakai Y, Uetsuka K, Asai Y, Kariya K, Nakayama H, Ohno K, Tsujimoto H
  • Journal Title: J Comp Pathol. (Submitted)
• [Journal Article] Plasma cell leukemia in a cat
  • Author(s): Takeuchi Y, Iizuka H, Kanemitsu H, Fujino Y, Nakashima K, Uchida K, Ohno K, Nakayama H, Tsujimoto H
  • Journal Title: J Feline Med Surg. (Submitted)
• [Journal Article] Assignment of the feline pim-1 and fit-1, common integration sites of feline leukemia virus to chromosome B2q21.3 and q32
  • Author(s): Fujino Y. et.al.
  • Journal Title: Cytogenet Genome Res (Submitted)
  • Peer Reviewed
• [Journal Article] Chromosomal mapping of feline leukemia virus insertions in cat lymphoid turnors
  • Author(s): Fujino Y. et al.
  • Journal Title: Vet Immunol Immunopathol (Submitted)
  • Peer Reviewed
• [Journal Article] Cytomorphological and immunological classification of feline lymphomas
  • Author(s): Chino J. et.al.
  • Journal Title: J Comp Pathol (Submitted)
  • Peer Reviewed
• [Journal Article] Plasma cell leukemia in a cat
  • Author(s): Takeuchi Y. et.al.
  • Journal Title: J Feline Med Surg (Submitted)
  • Peer Reviewed
• [Presentation] 東大動物医療センターにおける献血プログラム (2009)
  • Author(s): 藤野泰人
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
  • Year and Date: 2009-02-15
• [Presentation] リンパ造血系腫瘍における抗がん剤の使い方 (2009)
  • Author(s): 藤野泰人
  • Organizer: 平成20年度日本獣医師会学会年次大会
  • Place of Presentation: 岩手
• [Presentation] リンパ腫診療最前線〜細胞学的分類に基づく治療戦略とレスキュー療法〜 (2009)
  • Author(s): 藤野泰人
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] 輸血の適応と方法 (2009)
  • Author(s): 藤野泰人
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] 東京大学動物医療センターにおける献血プログラム (2009)
  • Author(s): 藤野泰人
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] 肝内動脈門脈瘻と診断された猫の1例 (2009)
  • Author(s): 巽永美子, 中島亘, 高橋雅, 藤野泰人, 大野耕一, 辻本元
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] ピルビン酸キナーゼ欠乏症と診断したアビシニアンの一例 (2009)
  • Author(s): 関敬泰, 藤野泰人, 高橋雅, 中島亘, 大野耕一, 辻本元
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] 胸腔内に肉腫様癌の発生が認められた猫の一例 (2009)
  • Author(s): 望月浩之, 高橋雅, 藤野泰人, リンダ・スラットマン, 内田和幸, 中山裕之, 辻本元
  • Organizer: 日本獣医内科学アカデミー・日本獣医臨床病理学会2009年大会
  • Place of Presentation: 東京
• [Presentation] 猫白血病ウイルス感染による造血系腫瘍におけるLinker-mediatedPCRを用いたプロウイルス組込部位検出およびクローナリティ解析 (2008)
  • Author(s): 李有晶, ほか
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
  • Year and Date: 2008-09-25
• [Presentation] 猫のリンパ腫における予後因子の検討 (2008)
  • Author(s): 中嶋眞弓ほか
  • Organizer: 日本獣医臨床病理学会2008年大会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2008-02-24
• [Presentation] 猫の骨髄異形成症候群および急性骨髄性白血病における予後の比較検討 (2008)
  • Author(s): 大平麻路ほか
  • Organizer: 日本獣医臨床病理学会2008年大会
  • Place of Presentation: 大宮ソニックシティ
  • Year and Date: 2008-02-24
• [Presentation] Detection of proviral integration sites by linker-mediated PCR in FeLV-related hemolymphatic neoplasms and its clinical application to analyze tumor clonality (2008)
  • Author(s): 李有晶, 藤野泰人, 後藤裕子, 大野耕一, 辻本元
  • Organizer: 第146回日本獣医学会学術集会
  • Place of Presentation: 宮崎
• [Presentation] 猫の各種疾患症例における血中チミジンキナーゼ活性測定とその臨床的有用性 (2008)
  • Author(s): 関敬泰, 藤野泰人, 平山健太郎, 高橋雅, 中島亘, 大野耕一, 辻本元
  • Organizer: 第29回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] 輸血療法のすべて (2008)
  • Author(s): 藤野泰人
  • Organizer: 第29回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] 消化管間質腫瘍が認められた猫の2例 (2008)
  • Author(s): 神徳幸子, 藤野泰人, 中島亘, 佐々木めぐみ, 上塚浩司, 中山裕之, 磯谷真弓, 盆子原誠, 大野耕一, 辻本元
  • Organizer: 日本獣医臨床病理学会2008年大会
  • Place of Presentation: 埼玉
• [Presentation] 猫のリンパ腫における予後因子の解析 (2008)
  • Author(s): 中嶋眞弓, 藤野泰人, 高橋雅, 中島亘, 大野耕一, 辻本元
  • Organizer: 日本獣医臨床病理学会2008年大会
  • Place of Presentation: 埼玉
• [Presentation] 猫の骨髄異形成症候群および急性骨髄性白血病における予後の比較検討 (2008)
  • Author(s): 大平麻路, 藤野泰人, 高橋雅, 中島亘, 大野耕一, 辻本元
  • Organizer: 日本獣医臨床病理学会2008年大会
  • Place of Presentation: 埼玉
• [Presentation] 猫のリンパ腫における細胞学的分類および免疫学的表現型に関する検討 (2007)
  • Author(s): 茅野順子ほか
  • Organizer: 第28回動物臨床医学会年次大会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2007-11-17
• [Presentation] 猫のリンパ腫における細胞学的分類および免疫学的表現型に関する検討 (2007)
  • Author(s): 茅野順子, 山崎淳平, 竹内由則, 後藤裕子, 苅谷和廣, 浅井洋子, 白井活光, 小林哲也, 坂井祐介, 上塚浩司, 中山裕之, 藤野泰人, 大野耕一, 辻本元
  • Organizer: 第28回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] 猫のDICにおける臨床的特徴 (2007)
  • Author(s): 神徳幸子, 岡部幹, 高橋雅, 中島亘, 藤野泰人, 大野耕一, 辻本元
  • Organizer: 第28回動物臨床医学会年次大会
  • Place of Presentation: 大阪
• [Presentation] 免疫介在性血液疾患の診断と治療 (2007)
  • Author(s): 藤野泰人
  • Organizer: 第4回日本獣医内科学アカデミー学術大会
  • Place of Presentation: 東京