Illegitimate V(D)J recombination as an MRD marker in acute lymphoblastic leukemia

• Project/Area Number: 17K16174
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Hokkaido University
• Principal Investigator: Okada Kohei 北海道大学, 医学研究院, 客員研究員 (30792501)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: V(D)J組み換え / 微小残存病変 / IKZF1欠失 / デジタルPCR / FISH / 血液腫瘍学

Outline of Final Research Achievements

V(D)J mediated IKZF1 deletion occurred frequently in acute lymphoblastic leukemia. IKZF1 deletion occurred only in leukemic cells and potentially become a marker detecting minimal residual disease. We developed FISH probe detecting all 4 different types of IKZF1 deletion. We verified the FISH method could detect IKZF1 deletion fast and easily in clinical samples. We found the samples which showed balletic IKZF1 deletion or insertion of the deleted IKZF1 fragment into immunoglobulin region. We also developed digital PCR method which quantitatively detect IKZF1Δ4-7 deletion.

Academic Significance and Societal Importance of the Research Achievements

急性リンパ性白血病において、FISHやデジタルPCRなどの簡便な検査により腫瘍特異的な変異を検出できる方法を確立した。IKZF1欠失は急性リンパ性白血病における予後不良因子として知られるが、これまで標準的な測定方法がなかった。白血病細胞の治療においては、微小残存病変がフォローできることで、治療効果が続いていることの確認や、再発の早期発見が可能となり、各症例の治療反応性に最適化した個別化治療が可能となる。FISHやデジタルPCRによるIKZF1欠失の検出はこのような微小残存病変マーカーとして有用と考えられる。

Research Products

• [Journal Article] Development of a Fluorescence in Situ Hybridization Probe for Detecting IKZF1 Deletion Mutations in Patients with Acute Lymphoblastic Leukemia (2018)
  • Author(s): Hashiguchi Junichi、Onozawa Masahiro、Oguri Satoshi、Fujisawa Shinichi、Tsuji Masahisa、Okada Kohei、Nakagawa Masao、Hashimoto Daigo、Kahata Kaoru、Kondo Takeshi、Shimizu Chikara、Teshima Takanori
  • Journal Title: The Journal of Molecular Diagnostics Volume: 20 Issue: 4 Pages: 446-454
  • DOI: 10.1016/j.jmoldx.2018.02.005
  • NAID: 120006649182
  • Peer Reviewed
• [Journal Article] Quantitative detection of IKZF1 deletion by digital PCR in patients with acute lymphoblastic leukemia (2018)
  • Author(s): Hashiguchi J, Onozawa M, Okada K, Amano T, Hatanaka KC, Nishihara H, Sato N, Teshima T
  • Journal Title: Int J Lab Hematol Volume: 41 Issue: 2
  • DOI: 10.1111/ijlh.12945
  • Peer Reviewed
• [Patent(Industrial Property Rights)] ＩＫＺＦ１遺伝子変異を検出するための核酸プローブセット及び当該プロ ーブセットを用いたＩＫＺＦ１遺伝子変異の検出方法 (2019)
  • Inventor(s): 小野澤真弘
  • Industrial Property Rights Holder: 小野澤真弘
  • Industrial Property Rights Type: 特許
  • Filing Date: 2019