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

Elucidating the mechanisms by which spliceosomal gene LUC7L2 defects causes myeloid neoplasms

Research Project

Project/Area Number 16K09844
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionUniversity of Fukui

Principal Investigator

Hosono Naoko  福井大学, 学術研究院医学系部門(附属病院部), 講師 (50509312)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨髄系腫瘍 / 7番染色体 / LUC7L2 / スプライシングの異常 / スプライシング異常 / HMGN1 / LETMD1 / U1snRNP / スプライシング / スプライスソーム / 骨髄系悪性腫瘍 / Luc7L2 / 癌 / 発現制御
Outline of Final Research Achievements

Deletions of the long arm of chromosome 7 are common karyotypic abnormalities in myeloid neoplasms and are associated with poor prognosis. LUC7L2, a putative U1 spliceosomal protein, is located in 7q34, which is deleted in 85% of -7/del7q patients. To clarify the role of LUC7L2 in myeloid neoplasms, we generated knocked down LUC7L2 in leukemic cell lines. Knockdown cells induced the formation of membrane blebs and adhere to each other. Expression analysis revealed increased expression of NOTCH3, AMIGO and ABLIM1 in knockdown cells. Skipping exon is most frequent alternative splicing event in knockdown cell, Mutually exclusive splicing event in HMGN1 were also seen in knockdown cell. Loss of function or low expression of LUC7L2 results in distinctly altered splicing patterns involving various kind of genes associated with cytoskeletal components, spliceosome, apoptosis or histone modification, and may collaborate to leukemogenesis.

Academic Significance and Societal Importance of the Research Achievements

骨髄系腫瘍でよくみられる異常であるLUC7L2の機能低下により、タンパク合成のステップの一つであるスプライシングの異常をきたし、その結果腫瘍の増殖に関わる多数の分子の発現が変化することが判明した。LUC7L2が介するこれらの分子の機能異常が、腫瘍化の原因および進展に関わることから、これらの分子を標的とした阻害物質の開発や、LUC7L2の機能を回復させる活性化物質の開発が、難治性骨髄系腫瘍の治療戦略になりうると期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Genetic abnormalities and pathophysiology of MDS2019

    • Author(s)
      Naoko Hosono
    • Journal Title

      International Journal of Clinical Oncology

      Volume: 印刷中 Issue: 8 Pages: 885-892

    • DOI

      10.1007/s10147-019-01462-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Spliceosomal gene LUC7L2 defect causes alteration of NOTCH3 and BIM expression in myeloid leukemia cell lines2018

    • Author(s)
      Naoko Hosono
    • Organizer
      The 9th JSH International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi