The role of megakaryocytic signals in Evi1 leukemia

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790961
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: The University of Tokyo
• Principal Investigator: OKOCHI Naoko 東京大学, 医学部附属病院, 助教 (00568412)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: Evi1 / leukemia / model mouse / CD41 / cMpl / TPO

Research Abstract

Ecotropic viral integration site 1 (Evi1), located on chromosome 3q26, is an independent negative prognostic indicator of survival in acute myeloid leukemia (AML). Thrombocytosis is a characteristic feature in AML patients with 3q26 abnormality, and the platelet function related genes, such as CD41 (integrin aIIb) and cMpl, positively correlates with Evi1 expression in AML patients. Previously, we succeeded in making a mouse model of Evi1-related leukemia. Sub-population of this Evi1 leukemia mice cells expressed both CD41 and cMpl. The CD41+ fraction of Evi1 leukemia mice more efficiently induced secondary leukemia than the CD41- counterpart in a serial BMT assay. The CD41+ cells predominantly expressed cMpl, and shRNA-mediated knockdown of cMpl delayed the progression of Evi1 leukemia in vivo, suggesting that THPO/cMpl signaling is involved in enhancing the growth and survival of Evi1 leukemia cells.

Research Products

• [Journal Article] Age-related epigenetic drift in the pathogenesis of MDS and AML (2014)
  • Author(s): Maegawa S, Gough SM, Watanabe-Okochi N, Lu Y, Zhang N, Castoro RJ, Estecio MR, Jelinek J, Liang S, Kitamura T, Aplan PD, Issa JP
  • Journal Title: Genome Res Volume: 24(4) Pages: 580-91
  • DOI: 10.1111/bjh.12726
• [Journal Article] Single-cell gene expression analysis reveals clonal architecture of blast-phase chronic myeloid leukaemia (2014)
  • Author(s): Nukina A, Kagoya Y, Watanabe-Okochi N, Arai S, Ueda K, Yoshimi A, Nannya Y, Kurokawa M
  • Journal Title: Br J Haematol Volume: (Epub ahead of print)
• [Journal Article] The role of alloantibodies against human platelet antigen-15 in multiply platelet transfused patients (2014)
  • Author(s): Matsuhashi M, Tsuno NH, Sone S, Mishima Y, Nagura Y, Watanabe-Okochi N, Ikeda T, Kashiwase K, Fukuda S, Iriyama T, Hyodo H, Yamashita T, Kamei Y, Arai S, Minami M, Fujii T, Kurokawa M, Tozuka M, Takahashi K, Santoso S
  • Journal Title: Transfusion Volume: 54(4) Pages: 1093-9
• [Journal Article] Safety and efficacy of preoperative autologous blood donation for high-risk pregnant women : experience of a large university hospital in Japan (2014)
  • Author(s): Yamamoto Y, Yamashita T, Tsuno NH, Nagamatsu T, Okochi N, Hyodo H, Ikeda T, Kawabata M, Kamei Y, Nagura Y, Sone S, Fujii T, Takahashi K, Kozuma S
  • Journal Title: J Obstet Gynaecol Res Volume: 40 Pages: 1308-16
• [Journal Article] The shortest isoform of C/EBPβ, Liver inhibitory protein (LIP), collaborates with Evi1 to induce AML in a mouse BMT model (2013)
  • Author(s): Watanabe-Okochi N, Yoshimi A, Sato T, Ikeda T, Kumano K, Taoka K, Satoh Y, Shinohara A, Tsuruta T, Masuda A, Yokota H, Yatomi Y, Takahashi K, Kitaura J, Kitamura T, Kurokawa M
  • Journal Title: Blood Volume: 121(20) Pages: 4142-55
• [Journal Article] Prediction model for CD34 positive cell yield in peripheral blood stem cell collection on the fourth day after G-CSF administration in healthy donors (2013)
  • Author(s): Yoshizato T, Watanabe-Okochi N, Nannya Y, Ichikawa M, Takahashi T, Sato T, Masuda A, Yatomi Y, Tsuno NH, Kurokawa M, Takahashi K
  • Journal Title: Int J Hematol Volume: 98(1) Pages: 56-65
• [Journal Article] A role for RUNX1 in hematopoiesis and myeloid leukemia (2013)
  • Author(s): Ichikawa M, Yoshimi A, Nakagawa M, Nishimoto N, Watanabe-Okochi N, Kurokawa M
  • Journal Title: Int J Hematol Volume: 97(Review) Pages: 726-34
• [Journal Article] The current status of autologous blood transfusion in Japan - The importance of pre-deposit autologous blood donation program and the needs to achieve patient blood management (2013)
  • Author(s): Tsuno NH, Nagura Y, Kawabata M, Matsuhashi M, Sone S, Ikeda T, Okochi N, Takahashi K
  • Journal Title: Transfus Apher Sci Volume: 49(3) Pages: 673-80
• [Journal Article] The frequencies of SLC44A2 alleles among the Japanese population (2013)
  • Author(s): Matsuhashi M, Tsuno NH, Ikeda T, Mishima Y, Watanabe-Okochi N, Santoso S, Tozuka M, Takahashi K
  • Journal Title: Tissue Antigens Volume: 81(4) Pages: 227-8
• [Journal Article] The shortest isoform of C/EBPβ, Liver inhibitory protein (LIP), collaborates with Evi1 to induce AML in a mouse BMT model (2013)
  • Author(s): Watanabe-Okochi N, Yoshimi A, Sato T, Ikeda T, Kumano K, Taoka K, Satoh Y, Shinohara A, Tsuruta T, Masuda A, Yokota H, Yatomi Y, Takahashi K, Kitaura J, Kitamura T, Kurokawa M
  • Journal Title: Rinsho Ketsueki Volume: 54(8) Pages: 749-58
• [Presentation] Evi1-induced leukemic cells express CD41 known as a megakaryocytic marker in a mouse BMT bone marrow transplantation model (2012)
  • Author(s): 大河内直子
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-14
• [Presentation] Evi1-induced leukemic cells express CD41 known as a megakaryocytic marker in a mouse BMT model (2012)
  • Author(s): 大河内直子
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
• [Book] 輸血合併症 : 今日の治療と看護 改訂第3版 (2013)
  • Author(s): 大河内直子, 高橋孝喜
  • Total Pages: 45-50