Elucidate the autonomous activation mechanism of thrombopoietin receptor without genetic mutation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08424
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Juntendo University
• Principal Investigator: Yang Yinjie 順天堂大学, 医学部, 非常勤助教 (90808643)
• Co-Investigator(Kenkyū-buntansha): 小松 則夫 順天堂大学, 医学部, 特任教授 (50186798) ; 今井 美沙 順天堂大学, 大学院医学研究科, 非常勤助教 (50709003) ; 荒木 真理人 順天堂大学, 大学院医学研究科, 客員教授 (80613843)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨髄増殖性腫瘍 / triple-negative / 造血幹細胞 / トロンボポエチン受容体

Outline of Final Research Achievements

This study aims to identify new markers effective for diagnosing triple-negative (TN) cases of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), in which three major diver mutations are not found. We conducted studies using Ba/F3-MPL-FR cells, a model of TN-MPNs that exhibit cytokine-independent activation of MPL. As a result, multiple genes involved in the autonomous proliferation of Ba/F3-MPL-FR cells were identified. These genes have not been previously reported to be associated with MPNs. This study is the first to suggest the possibility of a novel causing autonomous activation of MPL.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

骨髄増殖性腫瘍(MPNs)のうち、遺伝子変異の検出されないTN症例は診断に難渋することから、TN-MPN症例の診断に有効な新たなマーカーの同定と発症メカニズムの解明が求められている。本研究により明らかにされた遺伝子が、MPLの自律性活性化に関与することが明らかになれば、TN-MPN患者の診断や治療薬の開発の進展が大いに期待できる