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Analyses of cytokine responsive signaling of LPXN and enhanced responses caused by ETV6-LPXN

Research Project

Project/Area Number 25461437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionFujita Health University

Principal Investigator

ABE Akihiro  藤田保健衛生大学, 医学部, 客員准教授 (00432261)

Co-Investigator(Kenkyū-buntansha) NOBUHIKO Emi  藤田保健衛生大学, 血液内科, 教授 (30185144)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords染色体転座 / ETV6 / LPXN / G-CSF / CXCL12 / ETV6-LPXN / サイトカイン / RNA-seq / SDF1 / 細胞遊走 / ケモカイン / NUP98 / HOXA9
Outline of Final Research Achievements

LPXN acts as a signal transducing adaptor protein and plays important roles in cell adhesion and spreading. We discovered a novel fusion gene between ETV6 on 12p13 and LPXN on 11q12.1 in leukemic cells of a patient with relapsed acute myeloid leukemia. ETV6-LPXN did not transform the interleukin-3-dependent 32D myeloid cell line; however, an enhanced proliferative response was observed when these cells were treated with G-CSF without inhibition of granulocytic differentiation. The 32D and human leukemia cell lines each transduced with ETV6-LPXN showed enhanced migration towards the chemokine CXCL12. The immunofluorescence data indicated that ETV6-LPXN oligomerized, because it was detected as discrete spots in the cytoplasm, although LPXN was diffusively distributed throughout the cytoplasm. Our data indicate that ETV6-LPXN is associated with progression of leukemia through modulation of G-CSF and CXCL12/CXCR4, potentially acting within the microenvironment of leukemic cells.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013

All Journal Article (9 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (3 results)

  • [Journal Article] ETV6-LPXN fusion transcript generated by t(11;12)(q12.1;p13) in a patient with relapsing acute myeloid leukemia with NUP98-HOXA9.2016

    • Author(s)
      Abe A, Yamamoto Y, Iba S, Kanie T, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Mizuta S, Akatsuka Y, Okamoto M, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      Genes, chromosomes & cancer

      Volume: 55(3) Issue: 3 Pages: 242-250

    • DOI

      10.1002/gcc.22327

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional activation of platelet-derived growth factor receptor α and GS homeobox 2 resulting from E26 transformation-specific variant 6 translocation in a case of acute myeloid leukemia with t(4;12)(q12;p13).2016

    • Author(s)
      Abe A, Mizuta S, Okamoto A, Yamamoto Y, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      International journal of laboratory hematology

      Volume: 38(2) Issue: 2 Pages: 15-18

    • DOI

      10.1111/ijlh.12450

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] NUP214-RAC1 and RAC1-COL12A1 Fusion in Complex Variant Translocations Involving Chromosomes 6, 7 and 9 in an Acute Myeloid Leukemia Case with DEK-NUP214.2015

    • Author(s)
      Abe A, Yamamoto Y, Iba S, Okamoto A, Tokuda M, Inaguma Y, Yanada M, Morishima S, Kanie T, Tsuzuki M, Akatsuka Y, Mizuta S, Okamoto M, Kameyama T, Mayeda A, Emi N.
    • Journal Title

      Cytogenetic and genome research

      Volume: 146(4) Issue: 4 Pages: 279-284

    • DOI

      10.1159/000441464

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] t(11;21)(p14;q22) RUNX1/KIAA1549L2015

    • Author(s)
      Abe A
    • Journal Title

      Atlas Genet Cytogenet Oncol Haematol

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Journal Article] Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers.2014

    • Author(s)
      Yamamoto Y, Abe A, Emi N
    • Journal Title

      Molecular Cancer Research

      Volume: 12 Issue: 4 Pages: 479-84

    • DOI

      10.1158/1541-7786.mcr-13-0596

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Molecular Response to Nilotinib in a Patient with Imatinib-intolerant e19a2-positive Chronic Myeloid Leukemia.2014

    • Author(s)
      Kajiguchi T, Okuno S, Ohno T, Abe A.
    • Journal Title

      Intern Med.

      Volume: 53 Pages: 2801-2804

    • NAID

      130004713289

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A varicella outbreak in B-cell lymphoma patients receiving rituximab-containing chemotherapy.2014

    • Author(s)
      Okamoto A, Abe A, Okamoto M, Kobayashi T, Inaguma Y, Tokuda M, Yanada M, Morishima S, Kanie T, Yamamoto Y, Tsuzuki M, Mizuta S, Akatsuka Y, Yatsuya H, Yoshikawa T, Emi N.
    • Journal Title

      J Infect Chemother.

      Volume: 20 Issue: 12 Pages: 774-777

    • DOI

      10.1016/j.jiac.2014.08.006

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Functionally Deregulated AML1/RUNX1 Cooperates with BCR-ABL to Induce a Blastic Phase-Like Phenotype of Chronic Myelogenous Leukemia in Mice.2013

    • Author(s)
      Kiyoko Yamamoto, Shinobu Tsuzuki, Yosuke Minami, Yukiya Yamamoto, Akihiro Abe, Koichi Ohshima, Masao Seto, Tomoki Naoe.
    • Journal Title

      PLOS ONE

      Volume: 8 Issue: 9 Pages: e74864-e74864

    • DOI

      10.1371/journal.pone.0074864

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Injectable Bone Tissue Engineering Using Live Mesenchymal Stem Cells.2013

    • Author(s)
      Yamada Y, Nakamura S, Ito K, Umemura E, Hara K, Nagasaka T, Abe A, Baba S, Furuichi Y, Izumi Y, Klein OD, Wakabayashi T.
    • Journal Title

      Stem Cells

      Volume: 31 Issue: 3 Pages: 572-580

    • DOI

      10.1002/stem.1300

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] t(8;12;21)(q22:p12;q22)を有するRUNX1-RUNX1T1白血病に認められたTM7SF4-VPS13B融合遺伝子2015

    • Author(s)
      安部明弘、山本幸也、岡本晃直、徳田倍将、稲熊容子、山本起代子、柳田正光、森島聡子、蟹江匡治、赤塚美樹、水田秀一、岡本昌1、亀山俊樹2、前田 明、恵美宣彦
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢市
    • Year and Date
      2015-10-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] DEK-NUP214を有する急性骨髄性白血病に付加的に認められたNUP214-RAC1融合遺伝子2014

    • Author(s)
      安部明弘、恵美宣彦ら
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report
  • [Presentation] Molecular response to nilotinib in a patient with imatinib-intolerant e19a2 chronic myeloid leukemia2013

    • Author(s)
      梶口 智弘、奥野 真吾 、大野 稔人、安部 明弘
    • Organizer
      日本血液学会
    • Place of Presentation
      札幌
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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