Development of the novel genetic test for the leukemia after therapy and the analysis of its clinical significance

• Project/Area Number: 18K15390
• 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: Kobe University
• Principal Investigator: Shumpei Mizuta 神戸大学, 保健学研究科, 研究員 (10782138)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 微小残存病変 / 遺伝子検査 / 造血器腫瘍 / ゲノム解析 / IL3/IGH / 遺伝子異常の検出 / 白血病 / 治療効果判定

Outline of Final Research Achievements

Disease status of leukemia is judged by the type of genetic abnormalities and the degree of therapeutic effect, but there are a lot of genetic abnormalities and detecting method is not standardized. To provide optimal medicine for patients with leukemia, optimal genetic test is required depending on indivisual patients. This study was performed by focusing on the detection sensitivity and feasibility to enable genetic test even in the general hospitals. Introduction of the testing method proposed in this study will be expected to contribute to tailor-made medicine.

Academic Significance and Societal Importance of the Research Achievements

遺伝子異常は基本的にはgenomic DNAを用いられるが、キメラ遺伝子はRNAを用いて解析されることが一般的である。本研究では種々の造血器腫瘍においてgenomic DNA, RNAの両者を測定することで、上記の一般論が必ずしも適切ではなく、疾患に応じてより有用な方法を選択する重要性を示した。また、これまで遺伝子異常に基づいた治療後の検査が為されることがなかったIGH/IL3転座を伴う白血病の新規検査法を報告した。本研究内では一般病院でも実施可能であるかを重視して新規検査法を開発しており、将来的には遺伝子異常に基づいた診療を普及させる可能性がある。

Research Products

• [Journal Article] VS38 staining contributes to a novel gating strategy in flow cytometry for small B cell lymphoma, especially in lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (2021)
  • Author(s): Shumpei Mizuta, Noriko Yamane, Saya Mononobe, Asami Watanabe, Shinichiro Matsuki, Takao Komai, Yusuke Koba, Sachiko Mitani, Takahito Kawata, Akira Tamekane, Mitsumasa Watanabe
  • Journal Title: Cytometry Part B: Clinical Cytometry Volume: - Issue: 1 Pages: 50-61
  • DOI: 10.1002/cyto.b.22000
  • Peer Reviewed
• [Journal Article] cDNA-Based Mutation Screening Using a Combination of High-Resolution Melting Curve and Fragment Analysis Facilitates Efficient CCR4 Mutation Analysis in Adult T-Cell Leukemia/Lymphoma (2020)
  • Author(s): Shumpei Mizuta, Noriko Yamane, Saya Mononobe, Takao Komai, Yusuke Koba, Takahito Kawata, Naoya Ukyo, Akira Tamekane, Mitsumasa Watanabe
  • Journal Title: American Journal Of Clinical Pathology Volume: 154 Issue: 2 Pages: 236-241
  • DOI: 10.1093/ajcp/aqaa037
  • Peer Reviewed
• [Journal Article] Investigation of screening method for DNMT3A mutations by high‐resolution melting analysis in acute myeloid leukemia (2019)
  • Author(s): Mizuta Shumpei、Yamane Noriko、Komai Takao、Koba Yusuke、Kawata Takahito、Ukyo Naoya、Tamekane Akira、Watanabe Mitsumasa
  • Journal Title: International Journal of Laboratory Hematology Volume: 41 Issue: 5 Pages: 593-600
  • DOI: 10.1111/ijlh.13056
  • Peer Reviewed
• [Journal Article] VS38 as a promising CD38 substitute antibody for flow cytometric detection of plasma cells in the daratumumab era (2019)
  • Author(s): Mizuta Shumpei、Kawata Takahito、Kawabata Hiroshi、Yamane Noriko、Mononobe Saya、Komai Takao、Koba Yusuke、Ukyo Naoya、Tamekane Akira、Watanabe Mitsumasa
  • Journal Title: International Journal of Hematology Volume: 110 Issue: 3 Pages: 322-330
  • DOI: 10.1007/s12185-019-02685-z
  • Peer Reviewed
• [Journal Article] SF3B1変異と環状鉄芽球を伴う骨髄異形成症候群の関連性 (2019)
  • Author(s): 水田 駿平、山根 範子、物延 沙耶、川畑 宏志、渡邊 光正、駒井 隆夫
  • Journal Title: 日本検査血液学会学術雑誌 Volume: 20 Pages: 424-431
  • Peer Reviewed
• [Journal Article] フラグメント解析によるFLT3-ITD変異量解析の臨床的有用性 (2019)
  • Author(s): 山根 範子、水田 駿平、物延 沙耶、川畑 宏志、大谷 敦子、渡邊 光正、駒井 隆夫
  • Journal Title: 日本検査血液学会学術雑誌 Volume: 20 Pages: 216-223
  • Peer Reviewed
• [Journal Article] Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute lymphoblastic leukemia (2018)
  • Author(s): Kobayashi Kenichiro、Mizuta Shumpei、Yamane Noriko、Ueno Hiroo、Yoshida Kenichi、Kato Itaru、Umeda Katsutsugu、Hiramatsu Hidefumi、Suehiro Minoru、Maihara Toshiro、Usami Ikuya、Shiraishi Yuichi、Chiba Kenichi、Miyano Satoru、Adachi Souichi、Ogawa Seishi、Kiyokawa Nobutaka、Heike Toshio
  • Journal Title: Pediatric Blood & Cancer Volume: 66 Issue: 1
  • DOI: 10.1002/pbc.27449
  • Peer Reviewed
• [Journal Article] Evaluation of SF3B1 Mutation Screening by High-Resolution Melting Analysis and its Clinical Utility for Myelodysplastic Syndrome with Ring Sideroblasts at the Point of Diagnosis (2018)
  • Author(s): Mizuta Shumpei、Yamane Noriko、Komai Takao、Koba Yusuke、Ukyo Naoya、Tamekane Akira、Watanabe Mitsumasa
  • Journal Title: Laboratory Medicine Volume: 印刷中 Issue: 3 Pages: 254-262
  • DOI: 10.1093/labmed/lmy070
  • Peer Reviewed
• [Presentation] 抗体医薬時代における多発性骨髄腫のフローサイトメトリー解析 (2020)
  • Author(s): 水田 駿平
  • Organizer: 第21回日本検査血液学会学術集会
  • Invited
• [Presentation] NPM1変異mRNA定量PCRによる急性骨髄性白血病の病勢評価 (2019)
  • Author(s): 水田 駿平、物延 沙耶、大谷 敦子、川畑 宏志、駒井 隆夫
  • Organizer: 第68回日本医学検査学会
• [Presentation] t (5;14) (q31; q32) IL3/IGHを伴う急性リンパ性白血病の病態解析 (2019)
  • Author(s): 水田 駿平、小林 健一郎、山根 範子、物延 沙耶、川畑 宏志、駒井 隆夫
  • Organizer: 第20回日本検査血液学会学術集会
• [Presentation] A rapid screening method for DNMT3A mutations in acute myeloid leukemia by high-resolution melting analysis (2019)
  • Author(s): Shumpei Mizuta, Noriko Yamane, Takao Komai, Yusuke Koba, Takahito Kawata, Naoya Ukyo, Akira Tamekane, Mitsumasa Watanabe
  • Organizer: 第81回日本血液学会学術集会
• [Presentation] Lineage switch from early T-cell precursor acute lymphoblastic leukemia to acute monoblastic leukemia following treatment with nelarabine and a cord blood stem cell transplantation (2018)
  • Author(s): Mizuta Shumpeo, Yamane Noriko, Kobayashi Kenichiro, Suehiro Minoru, Maihara Toshiro, Usami Ikuya, Komai Takao, and Heike Toshio
  • Organizer: The 50th Annual Congress of the International Society of Paediatric Oncology
  • Int'l Joint Research
• [Presentation] Paraneoplastic hypereosinophilic syndrome associated with IL3-IgH positive acute lymphoblastic leukemia (2018)
  • Author(s): Kobayashi Kenichiro, Mizuta Shumpei, Yamane Noriko, Suehiro Minoru, Maihara Toshiro, Usami Ikuya, Heike Toshio
  • Organizer: The 50th Annual Congress of the International Society of Paediatric Oncology
  • Int'l Joint Research
• [Presentation] Utility of SF3B1 mutation screening at diagnosis for myelodysplastic syndrome with ring sideroblasts (2018)
  • Author(s): Mizuta Shumpei, Yamane Noriko, Komai Takao, Koba Yusuke, Kawata Takahito, Ukyo Naoya, Tamekane Akira, Watanabe Mitsumasa
  • Organizer: 第80回日本血液学会学術集会