Genetic and Transcriptional Landscape of Plasma Cells in POEMS Syndrome

• Project/Area Number: 26461397
• 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: Nakaseko Chiaki 千葉大学, 大学院医学研究院, 特任教授 (30323398)
• Co-Investigator(Kenkyū-buntansha): 堺田 恵美子 千葉大学, 医学部附属病院, 助教 (60422218)
• Co-Investigator(Renkei-kenkyūsha): MIMURA Naoya 千葉大学, 医学部付属病院, 助教 (00710229)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: POEMS症候群 / Whole exome sequencing / RNA sequencing / 次世代シークエンサー / VEGF / モノクローナル形質細胞 / Whole exome sequence / 骨髄微小環境 / 網羅的ゲノム解析 / 形質細胞増殖性疾患 / 形質細胞増殖疾患

Outline of Final Research Achievements

POEMS syndrome is a rare paraneoplastic disease associated with monoclonal plasma cells; however, the pathogenic importance of plasma cells is not clear. We performed comprehensive genetic analyses of plasma cells in patients with POEMS syndrome. A total of 359 somatic mutations in 334 genes were identified in 14 patients. None of the driver gene mutations frequently found in multiple myeloma (MM) were detected. Targeted sequencing of 52 selected genes identified 10 recurrently mutated genes. RNA sequencing revealed that the transcriptional profiles of POEMS syndrome were distinct from those of MGUS and MM. VEGF was not significantly upregulated and genes associated with tumorigenesis, such as MYC, were downregulated. We found that the genetic and transcriptional profiles of plasma cells in POEMS syndrome were distinct from those of other plasma cell disorders such as MM and MGUS, indicating unique properties of clonal plasma cells in the pathogenesis of POEMS syndrome.

Research Products

• [Journal Article] Safety and efficacy of granulocyte-colony stimulating factor monotherapy for peripheral blood stem cell collection in POEMS Syndrome. (2017)
  • Author(s): Muto T, Ohwada C, Takaishi K, Isshiki Y, Nagao Y, Hasegawa N, Kawajiri-Manako C, Togasaki E, Shimizu R, Tsukamoto S, Sakai S, Takeda Y, Mimura N, Takeuchi M, Sakaida E, Misawa S, Shimizu N, Iseki T, Kuwabara S, Nakaseko C.
  • Journal Title: Biol Blood Marrow Transplant Volume: 23 Issue: 2 Pages: 361-363
  • DOI: 10.1016/j.bbmt.2016.10.024
  • Peer Reviewed
• [Journal Article] Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis. (2016)
  • Author(s): Muto T, Ohwada C, Sawai S, Beppu M, Tsukamoto S, Takeda Y, Mimura N, Takeuchi M, Sakaida E, Sogawa K, Misawa S, Shimizu N, Iseki T, Nomura F, Kuwabara S, Nakaseko C.
  • Journal Title: Transfus Apher Sci Volume: 54 Issue: 2 Pages: 276-281
  • DOI: 10.1016/j.transci.2015.10.016
  • Peer Reviewed
• [Presentation] POEMS症候群におけるNGSを用いたλ鎖レパトア解析によるクローナルλ鎖再構成と疾患活動性の解析 (2017)
  • Author(s): 中世古知昭，真子千華，三村尚也，福世宏枝，福世真樹，永尾侑平，大島渚，塚本祥吉，高石浩司，酒井紫緒，竹田勇輔，大和田千桂子，武内正博，井関徹，三澤園子，桑原聡，金田篤志，堺田惠美子
  • Organizer: 第42回日本骨髄腫学会学術集会
  • Place of Presentation: 日本赤十字看護大学(東京都)
  • Year and Date: 2017-05-27
• [Presentation] POEMS症候群における形質細胞の網羅的遺伝子解析 (2017)
  • Author(s): 永尾侑平，三村尚也，竹田淳恵，大島基彦，吉田健一，堺田惠美子, 横手幸太郎, 桑原聡，眞田昌，岩間厚志，小川誠司，中世古知昭.
  • Organizer: 第54回日本臨床分子医学会学術集会
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2017-04-14
• [Presentation] Distinctive genetic features of plasma cells in POEMS syndrome. (2016)
  • Author(s): Nagao Y, Mimura N, Takeda J, Oshima M, Yoshida K, Shiozawa Y, Aoyama K, Saraya A, Koide S, Shiraishi Y, Chiba C, Tanaka H, Kawajiri-Manako C, Hasegawa N, Sakai S, Takeda Y, Ohwada C, Takeuchi M, Sakaida E, Iseki T, Misawa S, Yokote K, Miyano S, Ohara O, Kuwabara S, Sanada M, Iwama A, Ogawa S, Nakaseko C.
  • Organizer: The 58th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Diego Convention Center, San Diego, USA
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Clonal immunoglobulin λ light-chain gene rearrangements detected by next generation sequencing in POEMS Syndrome. (2016)
  • Author(s): Kawajiri-Manako C, Mimura N, Fukuyo M, Namba-Fukuyo H, Rahmutulla B, Nagao Y, Togasaki E, Shimizu R, Hasegawa N, Sakai S, Takeda Y, Ohwada C, Takeuchi M, Sakaida E, Iseki T, Misawa S, Yokote K, Tsuiji M, Kuwabara S, Kaneda A, Nakaseko C.
  • Organizer: The 58th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Diego Convention Center, 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
• [Presentation] Clonal IGL gene rearrangements detected by NGS is correlated with disease status in POEMS syndrome (2016)
  • Author(s): Chika Kawajiri, Naoya Mimura, Yuhei Nagao, Emi Togasaki, Ryo Shimizu, Nagisa Hasegawa, Yusuke Takeda, Shio Sakai, Chikako Ohwada, Masahiro Takeuchi, Emiko Sakaida, Tohru Iseki, Sonoko Misawa, Satoshi Kuwabara, Atsushi Kaneda, Chiaki Nakaseko
  • Organizer: 第78回日本血液学会総会
  • Place of Presentation: 神奈川県横浜市
  • Year and Date: 2016-10-13
• [Presentation] The Efficacy and Long-Term Outcomes of ASCT in POEMS Syndrome: A Multicenter Retrospective Study in Japan (2014)
  • Author(s): Chika Kawajiri, Emiko Sakaida, Chikako Ohwada, Toshihiro Miyamoto, Taichi Azuma, Jun Taguchi, Takehiko Mori, Yuichi Hasegawa, Tadakazu Kondo, Toshiaki Yujiri, Makoto Yoshimitsu, Mitsuru Tsudo, Toshihiko Iwasaki, Akio Shigematsu, Ritsuro Suzuki, Yoshiko Atsuta, Makoto Hirokawa, Hisashi Sakamaki, Chiaki Nakaseko.
  • Organizer: The 56th Annual Meeting of the American Society of Hematology
  • Place of Presentation: San Francisco
  • Year and Date: 2014-12-05 – 2014-12-09