Gene expression analysis of platelets and bone marrow stromal cells from patients with POEMS syndrome

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17850
• 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: Chiba University
• Principal Investigator: Tsukamoto Shokichi 千葉大学, 医学部附属病院, 助教 (00814617)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: POEMS症候群 / 骨髄間質細胞 / 血小板 / VEGF / RNAシークエンス

Outline of Final Research Achievements

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy or M protein, and skin changes (POEMS) syndrome is a rare monoclonal plasma cell disorder, with unique symptoms distinct from those of other plasma cell neoplasms, including high serum VEGF levels. This study focused mainly on bone marrow stromal cells (MSCs) as candidates for VEGF-producing cells in POEMS syndrome, and we aimed to analyze their gene expression and function.
MSCs that were obtained from patients with POEMS syndrome (n=9), were cultured, and were purified in vitro (POEMS-MSCs) showed no significant difference in VEGF mRNA expression compared to multiple myeloma (MM) MSCs (n=3), suggesting that VEGF-producing cells in POEMS syndrome are not bone marrow stromal cells. In addition, RNA sequencing analysis revealed that POEMS-MSCs (n=9) showed increased expression of gene clusters related to ossification and osteoblast differentiation compared to MM-MSCs (n=2) in gene ontology analysis.

Free Research Field

形質細胞性腫瘍

Academic Significance and Societal Importance of the Research Achievements

稀少難病であるPOEMS症候群は骨髄モノクローナル形質細胞の存在を基盤に発症していると考えられており、形質細胞異常の観点から多発性骨髄腫に対する新規薬剤の開発、導入により治療成績が向上しつつある。しかし、依然として治癒困難な疾患であり再発再燃を繰り返すため、患者救済のための総合的治療戦略は未解決と言える。本研究では形質細胞以外の治療標的細胞として骨髄間質細胞に着目しその遺伝子解析を行ったが、疾患特異的に高値を示すVEGFの産生細胞は骨髄間質細胞ではないことが示唆された結果であり、今後さらなる治療標的細胞の探索による病態解明が必要であると考えられた。