Establishment of treatment strategy for POEMS syndrome based on MRD detection method with next generation sequencer

• Project/Area Number: 15K09494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Chiba University
• Principal Investigator: Sakaida Emiko 千葉大学, 大学院医学研究院, 講師 (60422218)
• Co-Investigator(Kenkyū-buntansha): 中世古 知昭 千葉大学, 大学院医学研究院, 特任教授 (30323398) ; 武内 正博 千葉大学, 医学部附属病院, 助教 (50466702) ; 大和田 千桂子 千葉大学, 医学部附属病院, 助教 (80436352)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: POEMS症候群 / 次世代シークエンサー / 微小残存病変

Outline of Final Research Achievements

POEMS syndrome is a rare plasma cell dyscrasia. The pathogenesis is poorly understood, but monoclonal plasma cells are restricted and these immunoglobulin ramda light chain (IGL) V region genes are derived from only two germlines, either IGLV1-44 or 1-40. We analyzed the clonal IGLV gene rearrangements of genomic DNA samples of bone marrow mononuclear cells using next generation sequencing (NGS). The dominant clonal IGLV gene rearrangements clones of POEMS syndrome-specific germline sequences were significantly increased. In some cases, IGLV gene rearrangement clone was not detected as significant increase, but was detected using cDNA samples by heteroduplex analysis and Sanger sequencing, suggesting that the quite small number of monoclonal plasma cells may produce large quantity of mRNA of monoclonal proteins. Their clone sizes decreased and increased accompanying with disease status. The monitoring of clone size as MRD is useful for treatment decision in POEMS syndrome.

Research Products

• [Presentation] POEMS症候群に対する自家末梢血幹細胞移植療法 (2018)
  • Author(s): 堺田惠美子
  • Organizer: 第43回日本骨髄腫学会学術集会
  • Invited
• [Presentation] POEMS症候群における形質細胞の網羅的遺伝子解析 (2018)
  • Author(s): 三村尚也
  • Organizer: 第43回日本骨髄腫学会学術集会
  • Invited
• [Presentation] POEMS症候群の克服に向けて 分子病態解明と新規治療法の確立 (2018)
  • Author(s): 中世古知昭
  • Organizer: 第43回日本骨髄腫学会学術集会
  • Invited
• [Presentation] Clonal immunoglobulin λ light-chain gene rearrangements detected by next generation sequencing in POEMS Syndrome. (2016)
  • Author(s): Chika Kawajiri-Manako, Naoya Mimura, Masaki Fukuyo, Hiroe Namba-Fukuyo, Bahityar Rahmutulla, Yuhei Nagai, Yusuke Takeda, Chikako Ohwada, Masahiro Takeuchi, Emiko Sakaida, Sonoko Misawa, Koutaro Yokote, Satoshi Kuwabara, Atsushi Kaneda, Chiaki Nakaseko
  • Organizer: The 58th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Diego, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Clonal IGL gene rearrangements detected by NGS is correlated with disease status in POEMS syndrome (2016)
  • Author(s): 川尻千華, 三村尚也, 南波宏枝, 福世真樹, 永尾侑平, 東ヶ崎絵美, 清水亮, 竹田勇輔, 酒井紫緒, 大和田千桂子, 武内正博, 堺田惠美子, 井関徹, 三澤園子, 桑原聡, 築地信, 金田篤志, 中世古知昭.
  • Organizer: 第78回日本血液学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-10-13