Comprehensive proteomic analysis for inherited bone marrow failure syndrome.

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15601
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Nagoya University
• Principal Investigator: Wakamatsu Manabu 名古屋大学, 医学部附属病院, 助教 (00908882)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 遺伝性骨髄不全症候群 / プロテオミクス解析 / シュワッハマン・ダイアモンド症候群

Outline of Final Research Achievements

Recent advances in in-depth proteomic analysis have enabled comprehensive quantitative analysis of >10,000 protein. Herein, a proteogenomic analysis integrated with transcriptome analysis for IBMFS was performed to reveal their biological features. Unsupervised proteomic clustering identified eight independent clusters, with the ribosomal pathway specifically downregulated in C1 and C2, enriched for DBA and SDS, respectively. Four patients with ADH5/ALDH2 deficiency showed significantly reduced ADH5 protein expression. Six patients with SDS had significantly decreased SBDS protein expression. To provide a large-scale rapid screening system for IBMFS, targeted proteomic analysis was performed in 417 samples. SBDS and ADH5 protein expressions were significantly reduced in SDS and ADH5/ALDH2 deficiency, respectively. The clinical application of targeted proteomic assays would help diagnose and screen IBMFS for which appropriate clinical screening tests are lacking.

Free Research Field

小児血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

遺伝性骨髄不全症候群（IBMFS）は、全身臓器の合併症や若年成人期で発がん素因を有する疾患が含まれ、適切な治療やフォローアップを提供するために精緻な診断が必要である。従来、ゲノム解析のみでは半数以上のIBMFS患者で疾患表現型の原因遺伝子を同定することができず、遺伝子解析を補完する新たな診断システムの構築が望まれていた。本研究では、IBMFS関連タンパク質を搭載したパネルを作製し、標的プロテオミクス解析を行い、大規模かつ迅速にプロテオミクス解析を実行するシステムを構築した。小児期や若年性成人で急性骨髄性白血病や骨髄異形成症候群を発症した患者のスクリーニング検査として実用化が望まれる。