• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

The study to investigate mechanisms of B-cell homing to the microenvironment via DOCK2 and implications to the therapy far hematological malignancies

Research Project

Project/Area Number 18591036
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionHokkaido University

Principal Investigator

MITSUFUMI Nishio  Hokkaido University, Hokkaido University Hospital, Assistant Professor (10322801)

Co-Investigator(Kenkyū-buntansha) NISHIHARA Hiroshi  Hokkaido University, Graduate school of Medicine, Assistant professor (50322805)
Project Period (FY) 2006 – 2007
KeywordsDOCK2 / Chemotaxis / Ramos cell / SDF-1
Research Abstract

The purpose of this study was to investigate the role of DOCK2 in malignant B-cell homing to their microenvironment, as well as in the mechanisms of their survival in the microenvironment. At first, we tried to perform all experiments with primary human B cells. However, when we used those cells, there were too many dead cells just with introducing the DOCK2 siRNA. That made us to change our materials to Ramos, which is human B cell line. We have succeeded to obtain the stable DOCK2 knocked out Ramos with siRNA (ΔDOCK2 Ramos). The spontaneous growth of ΔDOCK2 Ramos appeared to be slightly slower than those transfected empty vector (MOCK Ramos). It was compatible that we saw the reduced ERK phospholyration in ΔDOCK2 Ramos. In addition, the chemotaxis toward SDF-1 was significantly reduced in ΔDOCK2 Ramos than those in MOCK Ramos.
Ramos expresses CD27, which is the marker for mature post germinal center memory B cells. It has been difficult to speculate the role of DOCK2 in those mature cells, as in the knock out mouse study, those mature cells could not differentiate from pre-germinal center B cells because of the luck of ability to home into germinal center. This study disclosed the important role of DOCK2 in the mature human B cells for their chemotaxis in the same way as those of mouse immature system. It has also suggested that DOCK2 might be involved in the survival pathway for human B cells.
At last, we could not see any differences in the expression levels of DOCK2 between human primary B cells and human malignant B cells, such as chronic lymphocytic leukemia, which may imply the difficulties simply to target DOCK2 in the treatment of B cell malignancies.

  • Research Products

    (9 results)

All 2007 2006

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (5 results)

  • [Journal Article] Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired in vitro immunoglobulin production in patients with non-Hodgkin lymphoma after rituximab treatment as an adjuvant to autologous stem cell transplantation2007

    • Author(s)
      Nishio M , et. al.
    • Journal Title

      British Journal of Haematology 137

      Pages: 349-354

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Reversible cardiomyopathy due to secondary hemochromatosis with multitransfusions for severe aplastic anemia after successful non-myeloablative stem cell transplantation.2007

    • Author(s)
      Nishio M , et. al.
    • Journal Title

      Int J of Cardiol

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Reversible cardiomyopathy due to secondary hemochromatosis with multitransfusions for severe aplastic anemia after successful non-myeloablative stem cell transplantation.2007

    • Author(s)
      Nishio M , et. al.
    • Journal Title

      Int J Cardiol

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma.2006

    • Author(s)
      Nishio M , et. al.
    • Journal Title

      European Journal of Haematology 77

      Pages: 226-232

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Presentation] 非ホジキンリンパ腫に対するリツキシマブ併用自家移植後の免疫グロブリン値とFCGR3A遺伝子多型2007

    • Author(s)
      西尾充史, 他
    • Organizer
      第69回日本血液学会総会・第49回日本臨床血液学会総会
    • Place of Presentation
      横浜市
    • Year and Date
      20071011-13
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The possible role of FCGR3A gene polymorphisms in the levels of serum Immunoglobulin after autologous stem cell transplantation with adjuvant rituximab2007

    • Author(s)
      Nishio , et. al.
    • Organizer
      The 69^<th> Annual meeting of the Japan Society of Hematology and the 49^<th> Annual meeting of the Japan clinical hematology
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      20071011-13
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired in vitro immunoglobulin G production in patients with non-Hodgkin lymphoma treated with rituximab.2006

    • Author(s)
      Nishio M , et. al.
    • Organizer
      The 48th Annual Meeting of American Society of Hematology
    • Place of Presentation
      Orlando, USA
    • Year and Date
      20061209-12
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] 非ホジキンリンパ腫に対する自家末梢血幹細胞移植後のrituximab投与に合併する低免疫グロブリン血症のmemory B細胞の回復遅延とアイソタイプ発現欠損2006

    • Author(s)
      西尾充史, 他
    • Organizer
      第28回日本造血細胞移植学会総会
    • Place of Presentation
      東京都
    • Year and Date
      20060204-05
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Hypogammaglobulinemia with a selective delayed recovery in memory B cells and an impaired isotype expression after rituximab administration as an adjuvant to autologous stem cell transplantation for non-Hodgkin lymphoma2006

    • Author(s)
      Nishio , et. al.
    • Organizer
      The 28th Annual Meeting of the Japan Society of Hematopoietic-cell transplantation
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20060204-05
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi