Epidemiological and molecular biological study of therapy-related myeloid neoplasms

• Project/Area Number: 16K09843
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kanazawa University
• Principal Investigator: OHTAKE SHIGEKI 金沢大学, その他部局等, その他 (00160523)
• Co-Investigator(Kenkyū-buntansha): 片桐 孝和 金沢大学, 保健学系, 助教 (60621159)
• Research Collaborator: MIYAZAKI yasushi ; KIYOI hitoshi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 治療関連骨髄性腫瘍 / 急性骨髄性白血病 / 骨髄異形成症候群 / 染色体異常 / キメラ遺伝子解析 / AML / MDS / CMMoL / 治療関連骨髄性腫瘍（t-MN） / 染色体核型 / 疫学的検討 / 癌 / 白血病

Outline of Final Research Achievements

We analyzed 3 databases of acute myeloid leukemia (AML) that was registered from all of the country. Frequency of therapy-related myeloid neoplasms(t-MN) was between 5.1 and 8.1%. Patients with t-MN were older than patients with de novo AML, and sex difference was not observed. Adverse cytogenetics were observed most frequently in patients with t-MN. Five years survival rate in patients with t-MN was significantly inferior to patients with de novo AML and was less than 20%. Survival probability in patients with t-MN might improve if they could receive intensive treatment.

Academic Significance and Societal Importance of the Research Achievements

化学療法や放射線療法後に出現する治療関連骨髄性腫瘍は近年増加しており、がん患者の予後が改善することに伴って注目されている。治療関連骨髄性腫瘍の疫学的特徴を10,000例以上の多数の症例が登録されたデータベースを用いて明らかにした。

Research Products

• [Journal Article] Clinical significance of ASXL2 and ZBTB7A mutations and C-terminally truncated RUNX1-RUNX1T1 expression in AML patients with t(8;21) enrolled in the JALSG AML201 study. (2019)
  • Author(s): Kawashima N, Akashi A, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kitamura K, Sakaida E, Takeshita A, Suzushima H, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H
  • Journal Title: Ann Hematol Volume: 98 Issue: 1 Pages: 83-91
  • DOI: 10.1007/s00277-018-3492-5
  • NAID: 120006623799
  • Peer Reviewed / Open Access
• [Journal Article] Tamibarotene maintenance improved relapse-free survival of acute promyelocytic leukemia: a final result of prospective, randomized, JALSG-APL204 study. (2019)
  • Author(s): Takeshita A, Asou N, Atsuta Y, Sakura T, Ueda Y, Sawa M, Dobashi N, Taniguchi Y, Suzuki R, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Furumaki H, Obata Y, Fujita H, Yanada M, Maeda Y, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Matsumura I, Naoe T, Miyazaki Y
  • Journal Title: Leukemia Volume: 33 Issue: 2 Pages: 358-370
  • DOI: 10.1038/s41375-018-0233-7
  • Peer Reviewed / Open Access
• [Journal Article] Infectious complications in adults undergoing intensive chemotherapy for acute myeloid leukemia in 2001–2005 using the Japan Adult Leukemia Study Group AML201 protocols (2018)
  • Author(s): Kato H, Fujita H, Akiyama N, Kimura SI, Hiramoto N, Hosono N, Takahashi T, Shigeno K, Minamiguchi H, Miyatake J, Handa H, Kanda Y, Yoshida M, Miyawaki S, Ohtake S, Naoe T, Kiyoi H, Matsumura I, Miyazaki Y
  • Journal Title: Support Care Cancer Volume: 26 Issue: 12 Pages: 4187
  • DOI: 10.1007/s00520-018-4292-0
  • Peer Reviewed / Open Access
• [Journal Article] Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia (2018)
  • Author(s): Kamijo Rena、Itonaga Hidehiro、Kihara Rika、Nagata Yasunobu、Hata Tomoko、Asou Norio、Ohtake Shigeki、Shiraishi Yuichi、Chiba Kenichi、Tanaka Hiroko、Miyano Satoru、Ogawa Seishi、Naoe Tomoki、Kiyoi Hitoshi、Miyazaki Yasushi
  • Journal Title: Leukemia Research Volume: 65 Pages: 34-41
  • DOI: 10.1016/j.leukres.2017.12.006
  • NAID: 120006988058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study (2018)
  • Author(s): Harada Y、Nagata Y、Kihara R、Ishikawa Y、Asou N、Ohtake S、Miyawaki S、Sakura T、Ozawa Y、Usui N、Kanamori H、Ito Y、Imai K、Suehiro Y、Kobayashi S、Kitamura K、Sakaida E、Onizuka M、Takeshita A、Ishida F、Suzushima H、Ishizawa K、Naoe T、Matsumura I、Miyazaki Y、Ogawa S、Kiyoi H
  • Journal Title: Leukemia Research Volume: 66 Pages: 20-27
  • DOI: 10.1016/j.leukres.2018.01.008
  • NAID: 120006473597
  • Peer Reviewed
• [Journal Article] Underweight status at diagnosis is associated with poorer outcomes in adult patients with acute myeloid leukemia: a retrospective study of JALSG AML 201 (2017)
  • Author(s): Harada Kaito、Doki Noriko、Hagino Takeshi、Miyawaki Shuichi、Ohtake Shigeki、Kiyoi Hitoshi、Miyazaki Yasushi、Fujita Hiroyuki、Usui Noriko、Okumura Hirokazu、Miyamura Koichi、Nakaseko Chiaki、Fujieda Atsushi、Nagai Tadashi、Yamane Takahisa、Sakamaki Hisashi、Ohnishi Kazunori、Naoe Tomoki、Ohno Ryuzo、Ohashi Kazuteru
  • Journal Title: Annals of Hematology Volume: 97 Issue: 1 Pages: 73-81
  • DOI: 10.1007/s00277-017-3156-x
  • Peer Reviewed
• [Journal Article] Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia (2017)
  • Author(s): Kuwatsuka Y、Asou N、Ohtake S、Miyawaki S、Miyazaki Y、Sakura T、Ozawa Y、Usui N、Kanamori H、Ito Y、Imai K、Suehiro Y、Kobayashi S、Kitamura K、Sakaida E、Ogawa S、Naoe T、Hayashi Y、Horibe K、Manabe A、Mizutani S、Adachi S、Kiyoi H et al.
  • Journal Title: International Journal of Hematology Volume: 107 Issue: 2 Pages: 201-210
  • DOI: 10.1007/s12185-017-2340-z
  • NAID: 120006473552
  • Peer Reviewed
• [Presentation] Clinical significance of ASXL2 and ZBTB7A mutations and AML1-ETO9a expression in AML with t(8;21): the JALSG AML201 study. (2018)
  • Author(s): Kawashima N, Ishikawa Y, Kiyoi H, Atsuta Y, Ohtake S, Asou N, Miyazaki Y, et al.
  • Organizer: International Society of Hematology. Annual Meeting.
  • Int'l Joint Research
• [Presentation] Prospective Evaluation of Prognostic Relevance of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia: Results from the JALSG CBF-AML209-KIT Study. (2018)
  • Author(s): Kawashima N, Ishikawa Y, Atsuta Y, Sugiura I, Sawa M, Dobashi N, Yokoyama H, Doki N, Tomita A, Kiguchi T, Koh S, Kanamori H, Iriyama N, Kohno A, Moriuchi Y, Asada N, Hirano D, Togitani K, Sakura T, Hagihara M, Tomikawa T, Yokoyama Y, Asou N, Ohtake S, Matsumura I, Miyazaki Y, Naoe T and Kiyoi H
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia Improved Long Term Relapse-Free Survival: 7-Year Results from a Randomized Controlled Trial, JALSG-APL204. (2017)
  • Author(s): Takeshita A, Asou N, Yanada M, Sakura T, Ueda Y, Sawa M, Dobashi N, Onizuka M, Taniguchi Y, Nakagawa M, Tamaki S, Hagihara M, Fujimaki K, Furumaki H, Fujita H, Usui N, Kobayashi Y, Kiyoi H, Ohtake S, Atsuta Y, Matsumura I, Naoe T and Miyazaki Y
  • Organizer: 第59回米国血液学会
  • Int'l Joint Research