Suppression of myeloproliferative neoplasm development by cleavage of mutant CALR

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16250
• 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: Kihara Yoshihiko 順天堂大学, 医学部, 博士研究員 (70812999)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄増殖性腫瘍 / カルレティキュリン / トロンボポエチン受容体 / 分子シャペロン / プロテアーゼ

Outline of Final Research Achievements

To elucidate the molecular mechanism of the specific cleavage that occurs in mutant Calreticulin (CALR) protein that causes Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), we identified proteases involved in the cleavage of mutant CALR. We further demonstrated that these proteases are also involved in the cleavage of mutant CALR in hematopoietic stem cells and megakaryocytic cells derived from MPN patients with CALR mutation.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、骨髄増殖性腫瘍(MPN)の発症原因分子である変異型CALR蛋白質の切断に関与するプロテアーゼを、世界に先駆けて同定した。このプロテアーゼを用いて、変異型CALR蛋白質の切断を利用した新規治療戦略の開発の可能性が示されたことから、学術的にも社会的にも意義深いと言える。