Elucidation of a novel mechanism of PBX2 molecule that functions in two ways: platelet signaling and megakaryocyte differentiation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K16984
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kagoshima University
• Principal Investigator: Obama Yuki 鹿児島大学, 鹿児島大学病院, 臨床検査技師 (50837276)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 血小板 / 血小板機能異常症 / PBX2

Outline of Final Research Achievements

This study attempts to elucidate the cause of the bleeding tendency in patients with undiagnosed bleeding tendency by identifying PBX2 as the responsible gene, which was discovered by exome analysis in the same family. Platelet aggregation test of the patient showed a half reduction in platelet aggregation with ADP stimulation and a lack of platelet aggregation with EPI stimulation. Platelet activation surface markers CD62P and PAC-I were measured using washed platelets, and the expression rate of PAC-I was reduced by one-third after TRAP and EPI stimulation in patients compared to controls.
These results suggest that PBX2 may be involved in the pathway after adenylate cyclase cycle (AC) activation, further increasing the presence of a novel pathway mediated by PBX2 within the platelet signaling pathway.

Free Research Field

内科学一般関連

Academic Significance and Societal Importance of the Research Achievements

本症例にて発見されたPBX2分子異常は世界初の報告である。
血小板凝集能試験結果および、洗浄血小板を用いた血小板活性化表面マーカーであるCD62P、PAC-I発現率の測定結果から得られた研究成果は、PBX2が血小板内シグナル経路のアデニル酸シクラーゼサイクル(AC)活性化後の経路内に関与する新たな知見へと繋がったことから、本邦における診断に至らない止血異常を有する血小板機能異常症患者の血小板機能の解明において、社会的意義は高いと言える。