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2007 Fiscal Year Final Research Report Summary

A novel therapy targeting Notch molecule against leukemia and a method to select patients suitable for the therapy

Research Project

Project/Area Number 18590522
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHUJI Tohda  Tokyo Medical and Dental University, Department of Laboratory Medicine, Associate Professor (80251510)

Project Period (FY) 2006 – 2007
KeywordsNotch / Leukemia / Molecular-targeting therapy / Gamma-secretase / Lymphoma / Myelodysplastic syndrome
Research Abstract

We previously reported that Notch signaling affected the growth of leukemia cells. Therefore, the regulation of the signaling can be a novel molecular-targeting therapy against leukemia. In this study, we examined molecular mechanism of Notch signaling in the growth of leukemia cells. We also examined the effects of Notch signal inhibitors on the growth.
We examined the effects of gamma-secretase inhibitors on the growth of cell lines derived from acute myeloid leukemia (AML), T-lymphoblastic leukemia (T-ALL), and B-cell lymphoma. We found that gamma-secretase inhibitors suppressed the growth of some cell lines, inducing apoptosis (Oncology Reports 2007). We have established a novel cell line derived from diffuse large B-cell lymphoma. This cell line showed constitutive activation of Notch signaling although it has no mutations in NOTCH1 gene. Gamma-secretase inhibitors suppressed the growth, inducing apoptosis (Leukemia Research 2006).
We have analyzed the mutations in NOTCH1 gene in 20 AML samples and found a missence mutation in PEST domain in one AML case. This case showed constitutive activation of Notch1 protein. We found that NOTCH1 mutations are rare in AML, while more than half of T-ALL have NOTCH1 mutations (Leukemia Lymphoma 2006). We also reported that NOTCH1 mutations was not observed in 20 MDS cases examined. Stimulation with Notch ligand protein slightly suppressed the colony formation (Leukemia Research 2007).
Taken together, we have shown that regulation of Notch signaling can be a molecular-targeting therapy against hematological malignancies such as leukemia.

  • Research Products

    (12 results)

All 2007 2006 Other

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Gamma-secretase inhibitors suppress the growth of Leukemia and lymphoma cells2007

    • Author(s)
      Kogoshi H, Sato T, Koyama T Nara N, Tohda S
    • Journal Title

      Oncology Reports 18

      Pages: 77-80

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Involvement of Notch signaling in myelodysplastic syndrome2007

    • Author(s)
      Fu L, Nara N, Tohda S
    • Journal Title

      Leukemia Research 31

      Pages: 1168-1169

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Gamma-secretase inhibitors suppress the growth of leukemia and lymphoma cells2007

    • Author(s)
      Kogoshi H, Sato T, Koyama T, Nara N, Tohda S.
    • Journal Title

      Oncology Reports 18

      Pages: 77-80

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Involvement of Notch signaling in myelodysplastic syndrome2007

    • Author(s)
      Fu L, Nara N, Tohda S.
    • Journal Title

      Leukemia Research 31

      Pages: 1168-1169

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Establishment of a novel B-cell lymphoma cell line with suppressed growth by gamma-secretase inhibitors2006

    • Author(s)
      Tohda S, Sato T, Kogoshi H, Fu L, Sakano S, Nara N
    • Journal Title

      Leukemia Research 30

      Pages: 1385-1390

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] NOTCH1 mutations are rare in acute myeloid leukemia2006

    • Author(s)
      Fu L, Kogoshi H, Nara N, Tohda S
    • Journal Title

      Leukemia and Lymphoma 47

      Pages: 2400-2403

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Establishment of a novel B-cell lymphoma cell line with suppressed growth by gamma-secretase inhibitors2006

    • Author(s)
      Tohda S, Sato T, Kogoshi H, Fu L, Sakano S, Nara N.
    • Journal Title

      Leukemia Research 30

      Pages: 1385-1390

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] NOTCH1 mutations are rare in acute myeloid leukemia2006

    • Author(s)
      Fu L, Kogoshi H, Nara N, Tohda S.
    • Journal Title

      Leukemia and Lymphoma 47

      Pages: 2400-2403

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Notchシグナル阻害剤による白血病・リンパ腫細胞の増殖抑制2007

    • Author(s)
      東田修二、小越英恵、付王路、星百合子
    • Organizer
      第54回日本臨床検査医学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-24
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Growth inhibition of leukemia and lymphoma cells by Notch signalling inhibitors2007

    • Author(s)
      Tohda S, Kogoshi H, Fu L, Hoshi Y.
    • Organizer
      54th meeting of Japanese Society of Laboratory Medicine
    • Place of Presentation
      Osaka
    • Year and Date
      2007-11-24
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 「疾患からまとめた病態生理FIRST AID」急性白血病など2007

    • Author(s)
      東田修二(分担執筆)
    • Total Pages
      380-411
    • Publisher
      メディカル・サイエンス・インターナショナル社
    • Description
      「研究成果報告書概要(和文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.tmd.ac.jp/med/mlab/mlab-J.html

URL: 

Published: 2010-02-04  

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