Elucidation of the molecular mechanism leading to the dysplasia of blood cells in the myelodysplastic syndromes

• Project/Area Number: 20590591
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Kawasaki Medical School
• Principal Investigator: TOHYAMA Kaoru Kawasaki Medical School, 医学部, 教授 (80227561)
• Co-Investigator(Kenkyū-buntansha): TASAKA Taizo 川崎医科大学, 医学部, 講師 (80343309) ; TSUJIOKA Takayuki 川崎医科大学, 医学部, 講師 (50330551)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血液学 / 遺伝子 / マイクロアレイ / プロテオーム / 細胞分化

Research Abstract

Aiming at the elucidation of the molecular mechanism leading to the dysplasia of blood cells in the myelodysplastic syndromes, we studied the effect of lenalidomide on MDS-L cell line which shows a deletion of chromosome 5q. As a result, MDS-L cells revealed an inhibition of cytokinesis and a reduction of gene expression of cell cycle-related genes including KIF20A which was located at chromosome 5q. RNA interference study suggested that inhibition of KIF20A expression affects the growth and morphology of blood cells.

Research Products

• [Journal Article] Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis. (2010)
  • Author(s): Matsuoka A, Tochigi A, Kishimoto M, Nakahara T, Kondo T, Tsujioka T, Tasaka T, Tohyama Y, Tohyama K
  • Journal Title: Leukemia 24 Pages: 748-755
  • Peer Reviewed
• [Journal Article] Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes. (2010)
  • Author(s): Tamura H, Dan K, Yokose N, Iwakiri R, Ohta M, Sakamaki H, Tohyama K, Kondo A, Hyodo H, Nakamura K, Yamashita T, Elisseeva OA, Oka Y, Oji Y, Sugiyama H, Ogata K
  • Journal Title: Leukemia Research 34 Pages: 986-990
  • Peer Reviewed
• [Journal Article] Multicenter phase II trial of vitamin K_2 monotherapy and vitamin K_2 plus 1α-hydroxyvitamin D_3 combination therapy for low-risk myelodysplastic syndromes. (2010)
  • Author(s): Akiyama N, Miyazawa K, Kanda Y, Tohyama K, Omine M, Mitani K, Ohyashiki K
  • Journal Title: Leukemia Research 34 Pages: 1151-1157
  • Peer Reviewed
• [Journal Article] Lenalidomide induces cell death in an MDS-derived cell line with deletion of chromosome 5q by inhibition of cytokinesis. (2010)
  • Author(s): Matsuoka A, et al.
  • Journal Title: Leukemia Volume: VOL.24 Pages: 748-755
  • Peer Reviewed
• [Journal Article] Prognostic significance of WT1 mRNA and anti-WT1 antibody levels in peripheral blood in patients with myelodysplastic syndromes. (2010)
  • Author(s): Tamura H, et al.
  • Journal Title: Leukemia Research Volume: VOL.34 Pages: 986-990
  • Peer Reviewed
• [Journal Article] Multicenter phase II trial of vitamin K_2 monotherapy and vitamin K_2 plus 1α-hydroxyvitamin D_3 combination therapy for low-risk myelodysplastic syndromes. (2010)
  • Author(s): Akiyama N, et al.
  • Journal Title: Leukemia Research Volume: VOL.34 Pages: 1151-1157
  • Peer Reviewed
• [Journal Article] Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes (MDS) with a deletion 5q abnormality. (2009)
  • Author(s): Harada H, Watanabe M, Suzuki K, Yanagita S, Suzuki T, Yoshida Y, Kimura A, Tsudo M, Matsuda A, Tohyama K, Taniwaki M, Takeshita K, Takatoku M, Ozawa K
  • Journal Title: International Journal of Hematology 90 Pages: 353-360
  • Peer Reviewed
• [Journal Article] MDS診療の最近の進歩「5q-症候群の責任遺伝子とレナリドマイドの分子作用機序」 (2009)
  • Author(s): 松岡亮仁、通山薫
  • Journal Title: 血液・腫瘍科 59 Pages: 33-39
• [Journal Article] Lenalidomide is active in Japanese patients with symptomatic anemia in low- or intermediate-1 risk myelodysplastic syndromes(MDS)with a deletion 5q abnormality (2009)
  • Author(s): Harada H, et al.
  • Journal Title: International Journal of Hematology 90 Pages: 353-360
  • Peer Reviewed
• [Journal Article] MDS診療の最近の進歩「5q-症候群の責任遺伝子とレナリドマイドの分子作用機序」 (2009)
  • Author(s): 松岡亮仁, 通山薫
  • Journal Title: 血液・腫瘍科 59 Pages: 33-39
• [Journal Article] Myelodysplastic syndrome (MDS) with chromosome 5 abnormalities : a nation-wide survey in Japan. (2008)
  • Author(s): Tasaka T, Tohyama K, Kishimoto M, Ohyashiki K, Mitani K, Hotta T, Kanamaru A, Okamoto S, Karasawa M, Kimura A, Tomonaga M, Uchiyama T, Ozawa K
  • Journal Title: Leukemia 22 Pages: 1874-1881
  • Peer Reviewed
• [Journal Article] High-resolution whole genome tiling path array CGH analysis of CD34^+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival. (2008)
  • Author(s): Starczynowski DT, Vercauteren S, Telenius A, Sung S, Tohyama K, Brooks-Wilson A, Spinelli JJ, Eaves CJ, Eaves AC, Horsman DE, Lam WL, Karsan A
  • Journal Title: Blood 112 Pages: 3412-3424
  • Peer Reviewed
• [Journal Article] Myelodysplastic syndrome (MDS) with chromosome 5 abnormalities : a nation-wide survey in Japan. (2008)
  • Author(s): Taizo Tasaka, et al.
  • Journal Title: Leukemia 22 Pages: 1874-1881
  • Peer Reviewed
• [Journal Article] High-resolut ion whole genome tiling path array CGH analysis of CD34^+cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts over all and leukemia-free survival. (2008)
  • Author(s): Daniel T. Starczynowski, et al.
  • Journal Title: Blood 112 Pages: 3412-3424
  • Peer Reviewed
• [Presentation] 難治性内科疾患の克服に向けて 8.特発性造血障害、特にMDSの診療と展望 (2010)
  • Author(s): 通山薫
  • Organizer: 日本内科学会学術集会 第38回内科学の展望
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2010-12-05
• [Presentation] 難治性内科疾患の克服に向けて 8.特発性造血障害、特にMDSの診療と展望 (2010)
  • Author(s): 通山薫
  • Organizer: 日本内科学会学術集会 第38回内科学の展望
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2010-12-05
• [Presentation] 骨髄異形成症候群のWHO-2008分類 (2009)
  • Author(s): 通山薫
  • Organizer: 第58回日本医学検査学会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-08-01
• [Presentation] 骨髄異形成症候群のWHO-2008分類 (2009)
  • Author(s): 通山薫
  • Organizer: 日本医学検査学会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-08-01
• [Presentation] 骨髄異形成症候群由来細胞株MDS-Lに対するlenalidomideの影響 (2008)
  • Author(s): 松岡亮仁、近藤敏範、辻岡貴之、中原貴子、栃木亜紀、田坂大象、通山薫
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 国立京都国際会館(京都市)
  • Year and Date: 2008-10-10
• [Presentation] 骨髄異形成症候群由来細胞株MDS-Lに対するlenalidomideの影響 (2008)
  • Author(s): 松岡亮仁, 他
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
• [Book] WHO血液腫瘍分類～WHO分類2008をうまく活用するために～ (2010)
  • Author(s): 通山薫(分担執筆)
  • Publisher: 医薬ジャーナル社
• [Book] WHO血液腫瘍分類～WHO分類2008をうまく活用するために～ (2010)
  • Author(s): 通山薫
  • Total Pages: 587
  • Publisher: 医薬ジャーナル社
• [Book] WHO分類第4版による白血病・リンパ系腫瘍の病態学 (2009)
  • Author(s): 通山薫(分担執筆)
  • Publisher: 中外医学社
• [Remarks] ホームページ等
  • URL: http://www.kawasaki-m.ac.jp/lh/
• [Remarks]
  • URL: http://www.kawasaki-m.ac.jp/lh/
• [Remarks] 川崎医科大学検査診断学教室オリジナルホームページ
  • URL: http://www.kawasaki-m.ac.jp/1h/
• [Remarks] 川崎医科大学検査診断学教室オリジナルホームページ
  • URL: http://www.kawasaki-m.ac.jp/1h/