charactarizing CD25 expressed CML stem cells

• Project/Area Number: 17K16199
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Karigane Daiki 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (60594588)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 慢性骨髄性白血病 / 微小残存病変 / 白血病幹細胞 / CD25

Outline of Final Research Achievements

The propotion of CD25 positive cells in hematopoietic stem proigenitor cell fraction positively correlated with thrombocytosis and anemia, suggesting that CD25 positive CML stem cells show unique proliferation and differentiation capacity. Tyrosine kinase inhibitors decrased these cells. We evaluated residual CD25 cells after treatment were used for detecting minimal residual disease in clinical examination because CD25 positive cells still existed after treatment. However, degital droplet PCR, which is the highest sensitivity and specificity method, did not find BCR-ABL fusion gene in residual CD25 positive cells. These findings suggested that the candidate surface stem cell marker which highly expresse at diagnosis should be evaluated after treatment.

Academic Significance and Societal Importance of the Research Achievements

慢性骨髄性白血病は特効薬により予後が劇的に改善した。しかしその特効薬は高価かつ催奇形性も報告されており、内服継続する事は多くの意味で負担がかかる。そのため疾患の源である白血病幹細胞の根絶療法開発が急務である。今回は治療前に慢性骨髄性白血病幹細胞に高く発現しているCD25に注目し、治療前・治療後の意味を検討した。治療前ではCD25陽性細胞の率と血小板数・貧血の程度が相関し、増殖率の高い特殊な細胞である事を示していた。一方で治療後にもCD25陽性細胞は存在しているが、これはCML細胞でない事が我々の研究で明らかとなった。治療前に高発現のものが全て治療後にも標的になる訳ではない事を示した。

Research Products

• [Presentation] CML幹前駆細胞分画におけるCD25発現の評価 (2018)
  • Author(s): 雁金大樹、笠原秀範、櫻井政寿、松木絵里、戸澤圭一、甲田祐也、外山高朗、菊池拓、加藤淳、清水隆之、森毅彦、矢作かおり、谷田部陽子、荒井智子、片桐尚子、清水長子、村田満、小林央、田久保圭誉、岡本真一郎
  • Organizer: 第78回日本血液学会学術集会
• [Presentation] Correlation of Expression of CD25 in Hematopoietic Stem/Progenitor Cell Fraction of Bone Marrow Cells with Response to Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia Patients (2018)
  • Author(s): Karigane D, Kasahara H, Sakurai M, Matsuki E, Tozawa K, Toyama T, Kikuchi T, Kato J, Shimizu T, Mori T, Yahagi K, Yatabe Y, Arai T, Katagiri N, Shimizu N, Mitsuhashi Y, Murata M, Kobayashi H, Takubo K, Okamoto S
  • Organizer: 58th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Evaluation and Significance of CD25 Expression in Hematopoitic Stem/Progenitor Cell Fraction of Bone Marrow Cells in Chronic Myelogenous Leukemia Patients (2018)
  • Author(s): Kasahara H, Karigane D, Yamazaki R, Fujita S, Shiroshita K, Sakurai M, Koda Y, Kikuchi T, Kato J, Shimizu T, Mori T, Yatabe Y, Arai T, Murata M, Kobayashi H, Takubo K, Okamoto S
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Correlation of Expression of CD25 in Hematopoietic Stem/Progenitor Cell Fraction of Bone Marrow Cells with Response to Tyrosine Kinase Inhibitors in Chronic Myelogenous Leukemia Patients (2018)
  • Author(s): Kasahara H, Karigane D, Okamoto S, Takubo K
  • Organizer: Highlights of American Society of Hematology in Asia-Pacific
  • Int'l Joint Research