Investigation of novel prognostic factors in acute myeloid leukemia using the purification system of leukemic cells

• Project/Area Number: 16K19193
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Kyoto University
• Principal Investigator: Matsuo Hidemasa 京都大学, 医学研究科, 助教 (80769737)
• Project Period (FY): 2016-04-01 – 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 白血病 / 予後因子 / レーザーマイクロダイセクション / 次世代シークエンス / CXCR4 / G-CSFR / CCND3 / CDK4/6 / MLL再構成 / 急性骨髄性白血病 / 遺伝子変異 / 遺伝子 / 次世代シーケンス

Outline of Final Research Achievements

A novel method to purify leukemic cells from blood smears based on the blood cell morphology was established (Int J Hematol. 2017;106(1):55-59.). CXCR4 overexpression was identified as a poor prognostic factor in pediatric acute myeloid leukemia (AML) with low risk (Pediatr Blood Cancer. 2016;63(8):1394-9.). In both pediatric and adult MLL-rearranged AML, novel CCND3 mutations were identified and CDK4/6 inhibition was shown as a promising therapeutic strategy. Moreover, the presence of coexisting mutations was a poor prognostic factor in MLL-rearranged AML (Blood Adv. 2018;2(21):2879-2889.).

Academic Significance and Societal Importance of the Research Achievements

急性骨髄性白血病(AML)の予後は、遺伝子・染色体異常等に基づく治療層別化により改善してきた。しかし、依然として難治・再発例がみられ、それらの予後は不良であるため、さらなる治療層別化につながる新規予後因子の同定が必要である。本研究により新規予後因子・治療ターゲットが同定され、さらに、より正確な予後因子解析を可能とする手法が開発されたことで、今後AML患者の治療成績向上に寄与すると考えられる。

Research Products

• [Journal Article] Introduce My Article (2019)
  • Author(s): 松尾英将
  • Journal Title: 臨床血液 Volume: 60:3 Pages: 256-256
• [Journal Article] Progressive Restrictive Ventilatory Impairment in Idiopathic Diffuse Pulmonary Ossification (2018)
  • Author(s): Matsuo H, Handa T, Tsuchiya M, Kubo T, Yoshizawa A, Nakayama Y, Shiga S, Hitomi T, Adachi S, Date H, Hirai T, Ichiyama S.
  • Journal Title: Internal Medicine Volume: 57 Issue: 11 Pages: 1631-1636
  • DOI: 10.2169/internalmedicine.9433-17
  • NAID: 130007382812
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-06-01
  • Peer Reviewed / Open Access
• [Journal Article] Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia (2018)
  • Author(s): Matsuo Hidemasa、Itonaga Hidehiro、et al.
  • Journal Title: Blood Advances Volume: 2 Issue: 21 Pages: 2879-2889
  • DOI: 10.1182/bloodadvances.2018019398
  • NAID: 120006534600
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Monitoring of fusion gene transcripts to predict relapse in pediatric acute myeloid leukemia. (2018)
  • Author(s): Matsuo H, Iijima-Yamashita Y, Yamada M, Deguchi T, Kiyokawa N, Shimada A, Tawa A, Tomizawa D, Taga T, Kinoshita A, Adachi S, Horibe K.
  • Journal Title: Pediatr Int. Volume: 60(1) Issue: 1 Pages: 41-46
  • DOI: 10.1111/ped.13440
  • Peer Reviewed
• [Journal Article] Multiplex fusion gene testing in pediatric acute myeloid leukemia. (2018)
  • Author(s): Iijima-Yamashita Y, Matsuo H, Yamada M, Deguchi T, Kiyokawa N, Shimada A, Tawa A, Takahashi H, Tomizawa D, Taga T, Kinoshita A, Adachi S, Horibe K.
  • Journal Title: Pediatr Int. Volume: 60(1) Issue: 1 Pages: 47-51
  • DOI: 10.1111/ped.13451
  • Peer Reviewed
• [Journal Article] Genetic regulation of the RUNX transcription factor family has antitumor effects. (2017)
  • Author(s): Morita K, Suzuki K, Maeda S, Matsuo A, Mitsuda Y, Tokushige C, Kashiwazaki G, Taniguchi J, Maeda R, Noura M, Hirata M, Kataoka T, Yano A, Yamada Y, Kiyose H, Tokumasu M, Matsuo H, Tanaka S, Okuno Y, Muto M, Naka K, Ito K, Kitamura T, Kaneda Y, Liu PP, Bando T, Adachi S, Sugiyama H, Kamikubo Y.
  • Journal Title: J Clin Invest. Volume: 127(7) Issue: 7 Pages: 2815-2828
  • DOI: 10.1172/jci91788
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fludarabine, cytarabine, granulocyte colony-stimulating factor and idarubicin for relapsed childhood acute myeloid leukemia. (2017)
  • Author(s): Nakayama H, Tomizawa D, Tanaka S, Iwamoto S, Shimada A, Saito AM, Yamashita Y, Moritake H, Terui K, Taga T, Matsuo H, Kosaka Y, Koh K, Hosoi H, Kurosawa H, Isoyama K, Horibe K, Mizutani S, Adachi S.
  • Journal Title: Pediatr Int. Volume: 59(10) Issue: 10 Pages: 1046-1052
  • DOI: 10.1111/ped.13378
  • Peer Reviewed
• [Journal Article] Autonomous feedback loop of RUNX1-p53-CBFB in acute myeloid leukemia cells. (2017)
  • Author(s): Morita K, Noura M, Tokushige C, Maeda S, Kiyose H, Kashiwazaki G, Taniguchi J, Bando T, Yoshida K, Ozaki T, Matsuo H, Ogawa S, Liu PP, Nakahata T, Sugiyama H, Adachi S, Kamikubo Y.
  • Journal Title: Sci Rep. Volume: 7(1) Issue: 1 Pages: 16604-16604
  • DOI: 10.1038/s41598-017-16799-z
  • NAID: 120006368172
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Purification of leukemic blast cells from blood smears using laser microdissection. (2017)
  • Author(s): Matsuo H, Shiga S, Imai T, Kamikubo Y, Toki T, Terui K, Ito E, Adachi S.
  • Journal Title: Int J Hematol. Volume: 印刷中 Issue: 1 Pages: 55-59
  • DOI: 10.1007/s12185-017-2227-z
  • Peer Reviewed
• [Journal Article] CXCR4 overexpression is a poor prognostic factor in pediatric acute myeloid leukemia with low risk: a report from the Japanese Pediatric Leukemia/Lymphoma Study Group (2016)
  • Author(s): Matsuo H, Nakamura N, Tomizawa D, Saito AM, Kiyokawa N, Horibe K, Nishinaka-Arai Y, Tokumasu M, Itoh H, Kamikubo Y, Nakayama H, Kinoshita A, Taga T, Tawa A, Taki T, Tanaka S, Adachi S
  • Journal Title: Pediatr Blood Cancer Volume: 63 Issue: 8 Pages: 1394-1399
  • DOI: 10.1002/pbc.26035
  • Peer Reviewed
• [Journal Article] 小児急性骨髄性白血病の分子的理解と臨床応用 (2016)
  • Author(s): 松尾英将、足立壯一
  • Journal Title: 血液フロンティア Volume: 26 Pages: 1513-21
• [Presentation] Recurrent genomic aberrations of D-type cyclins are therapeutic targets of CDK4/6 inhibitors in t(8;21) and MLL-rearranged acute myeloid leukemia (2018)
  • Author(s): Hidemasa Matsuo, Kenichi Yoshida, Kazutaka Fukumura, ... , Yasuhiko Kamikubo, Seishi Ogawa, Souichi Adachi
  • Organizer: 60th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Comprehensive Analysis of 343 Genes Using Targeted Sequencing Panel By Next-Generation Sequencer in 77 Pediatric AML Patients with Normal and Complex Karyotypes: Jccg Study, JPLSG AML-05 (2018)
  • Author(s): Taeko Kaburagi, Genki Yamato, Norio Shiba, Kenichi Yoshida, Yusuke Hara, Yuichi Shiraishi, Kentaro Ohki, Manabu Sotomatsu, Hirokazu Arakawa, Hidemasa Matsuo, Akira Shimada, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Keizo Horibe, Satoru Miyano, Seishi Ogawa, Souichi Adachi, Yasuhide Hayashi
  • Organizer: 60th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Landscape and prognostic significance of coexisting mutations in pediatric MLL-rearranged AML (2018)
  • Author(s): Hidemasa Matsuo, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Hiroo Ueno, Nobutaka Kiyokawa, Daisuke Tomizawa, Takashi Taga, Akio Tawa, Satoru Miyano, Yasuhiko Kamikubo, Seishi Ogawa, Souichi Adachi
  • Organizer: The 33rd World Congress of Biomedical Laboratory Science (IFBLS)
  • Int'l Joint Research
• [Presentation] Identification of recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia (2018)
  • Author(s): Hidemasa Matsuo, Kenichi Yoshida, Kazutaka Fukumura, ... , Yasuhiko Kamikubo, Seishi Ogawa, Souichi Adachi
  • Organizer: 第80回日本血液学会学術集会
• [Presentation] The detection of minor clones with somatic KIT D816V mutations in pediatric de novo AML (2018)
  • Author(s): Koji Sasaki, Norio Shiba, Yuri Uchiyama, Junji Ikeda, Masahiro Yoshitomi, Yuko Shimosato, Mayu Tokumasu, Hidemasa Matsuo, ... , Naomichi Matsumoto, Shuichi Ito, Yasuhide Hayashi
  • Organizer: 第80回日本血液学会学術集会
• [Presentation] Analysis of the functional role of CBFB in leukemogenesis (2018)
  • Author(s): Mina Noura, Ken Morita, Hidemasa Matsuo, Hiroshi Sugiyama, Yasuhiko Kamikubo, Souichi Adachi
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] Cell-Autonomous Feedback Loop of RUNX1-p53-CBFB in Acute Myeloid Leukemia Cells. (2017)
  • Author(s): Mina Noura, Ken Morita, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Toshikazu Bando, Kenichi Yoshida, Hidemasa Matsuo, Seishi Ogawa, Paul P. Liu, Hiroshi Sugiyama, Yasuhiko Kamikubo, and Souichi Adachi
  • Organizer: 59th ASH Annual Meeting and Exposition
  • Int'l Joint Research
• [Presentation] Distribution of the driver mutations among blood cell compartments in MDS and AML. (2016)
  • Author(s): Matsuo H, Ueno H, Yoshida K, Shiraishi Y, Tanaka H, Chiba K, Wakita T, Ohmori K, Hiramatsu H, Kawabata H, Takaori-Kondo A, Kamikubo Y, Miyano S, Ogawa S, Adachi S.
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-13
• [Presentation] Experience of the first certification of ISO15189:2012 in physiological examination in Japan. (2016)
  • Author(s): Matsuo H, Suzuki K, Iwata K, Yoneda T, Nakayama Y, Higuchi T, Shiga S, Ichiyama S.
  • Organizer: The 32nd World Congress of Biomedical Laboratory Science.
  • Place of Presentation: 神戸
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Remarks] 京都大学大学院医学研究科人間健康科学系専攻検査応用開発学分野 血液・生体防御学研究室ホームページ
  • URL: https://adachilab-kyotouniv.amebaownd.com/
• [Remarks] 急性骨髄性白血病の新規遺伝子変異を発見 －乳がんの既存薬が治療に有効である可能性－
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2018/181101_1.html
• [Remarks] 白血病、既存の乳がん薬が効果 京大が遺伝子変異特定
  • URL: https://www.nikkei.com/article/DGXMZO37173800R31C18A0000000/
• [Remarks] 京都大学大学院医学研究科人間健康科学系専攻 血液・生体防御学研究室
  • URL: http://adachilab.web.fc2.com/index.html