Search for target molecules for myeloproliferative neoplasms

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16098
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Juntendo University
• Principal Investigator: Masubuchi Nami 順天堂大学, 医学(系)研究科(研究院), 特任助教 (00791641)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 骨髄増殖性腫瘍 / calreticulin / 分子シャペロン / トロンボポエチン受容体

Outline of Final Research Achievements

This study showed followings: 1) the calreticulin mutant gene product found in Philadelphia chromosome-negative myeloproliferative neoplasms binds to the N-glycan of the thrombopoietin receptor (MPL) in the secretory pathway; 2) mutant CALR activates MPL on cell surface; and 3) thus, mutant CALR induces oncogenic transformation of the cells in a manner dependent on MPL.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、「変異型の分子シャペロンが、サイトカイン受容体のアゴニストとして下流シグナルを恒常的に活性化することで細胞を腫瘍化する」という腫瘍生物学の新概念が明らかになった。