Elucidation of significance of multiple genetic abnormalities and mechanism of acute transformation in myeloproliferative neoplasms

• Project/Area Number: 15K19554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Miyazaki
• Principal Investigator: Kameda Takuro 宮崎大学, 医学部, 医員 (30468029)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨髄増殖性腫瘍 / 急性転化 / JAK2

Outline of Final Research Achievements

We generated mouse models having genetic abnormalities of JAK2 mutation (JAK2V617F), TET2 deficiency, CBFb-MYH11 fusion gene in double to triple. In the double abnormal models (JAK2/TET2 compound model and JAK2/CBFb-MYH11 compound model), acute transformation did not occur. In conclusion, two or more additional abnormalities are required for the acute transformation of JAK2 mutant myeloproliferative neoplasms. The triple abnormal model was created and analysis was started.

Research Products

• [Journal Article] Differences in Hematological and Clinical Features Between Essential Thrombocythemia Cases With JAK2- or CALR-Mutations. (2017)
  • Author(s): Kubuki Y, Shide K, Kameda T, Yamaji T, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Hashimoto K, Yamamoto S, Hasuike S, Hidaka T, Nagata K, Kitanaka A, Shimoda K
  • Journal Title: Annals of laboratory medicine. Volume: 37 Issue: 2 Pages: 159-161
  • DOI: 10.3343/alm.2017.37.2.159
  • Peer Reviewed / Open Access
• [Journal Article] <i>TET2</i> mutation in diffuse large B-cell lymphoma (2017)
  • Author(s): Kubuki Y, Yamaji T, Hidaka T, Kameda T, Shide K, Sekine M, Kamiunten A, Akizuki K, Shimoda H, Tahira Y, Nakamura K, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta M, Yamamoto S, Hasuike S, Nagata K, Kitanaka A, Shimoda K
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 56 Issue: 3 Pages: 145-149
  • DOI: 10.3960/jslrt.56.145
  • NAID: 130005465221
  • ISSN: 1346-4280, 1880-9952
  • Peer Reviewed
• [Journal Article] 遺伝子解析に基づくがん治療 骨髄増殖性腫瘍(MPN/CML) (2016)
  • Author(s): 久冨木庸子、下田和哉
  • Journal Title: がん分子標的治療Vol.14 No.1 Volume: 14 Pages: 49-53
  • Peer Reviewed
• [Journal Article] Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib (2016)
  • Author(s): Kotaro Shide, Takuro Kameda, Takumi Yamaji, Masaaki Sekine, Naoki Inada, Ayako Kamiunten, Keiichi Akizuki, Kenichi Nakamura, Akira Kitanaka, Arata Honda, Akira Sawaguchi, Hiroo Abe, Tadashi Miike, Hisayoshi Iwakiri, Yoshihiro Tahara, Mitsue Sueta, Satoru Hasuike, Shojiro Yamamoto, Kenji Nagata, and Kazuya Shimoda
  • Journal Title: Leukemia Volume: 31 Issue: 5 Pages: 1136-1144
  • DOI: 10.1038/leu.2016.308
  • Peer Reviewed / Open Access
• [Journal Article] 骨髄増殖性腫瘍のWHO分類 (2016)
  • Author(s): 久冨木庸子、下田和哉
  • Journal Title: 日本臨牀増刊号 Volume: 74 Pages: 381-385
  • Peer Reviewed
• [Journal Article] Approach to special issues associated with myeloproliferative neoplasms (2015)
  • Author(s): 亀田 拓郎, 幣 光太郎, 久冨木 庸子
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 8 Pages: 972-980
  • DOI: 10.11406/rinketsu.56.972
  • NAID: 130005096290
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Functional analysis of TET2 using a knockdown mouse model (2015)
  • Author(s): 幣光太郎、亀田拓郎、下田和哉
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 6 Pages: 657-665
  • DOI: 10.11406/rinketsu.56.657
  • NAID: 130005093100
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Genetic and epigenetic abnormalities in myeloproliferative neoplasms (2015)
  • Author(s): 亀田拓郎、幣光太郎、下田和哉
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 6 Pages: 614-622
  • DOI: 10.11406/rinketsu.56.614
  • NAID: 130005093094
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Presentation] Mogamulizumab for adult T-cell leukemia/lymphoma in clinical practice. (2016)
  • Author(s): Masaaki Sekine, Yoko Kubuki, Takuro Kameda, Masaki Takeuchi, Takanori Toyama, Noriaki Kawano, Kouichi Maeda, Siichi Sato, Junzo Ishizaki, Hiroshi Kawano, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Kotaro Shide, Tomonori Hidaka, Akira Kitanaka, Kiyoshi Yamashita, Hitoshi Matsuoka, Kazuya Shimoda
  • Organizer: 58th ASH Annual Meeting & Exposition
  • Place of Presentation: サンディエゴ（アメリカ合衆国）
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] Physiological Expression of Calr Mutant Increases Cell Growth and Cytokine Independency in Human Cell Lines Expressing Mpl, and Develops Essential Thrombocythemia in Mice. (2016)
  • Author(s): Kotaro Shide, Takuro Kameda, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Tomonori Hidaka, Yoko Kubuki, Arata Honda, Akira Sawaguchi, Akira Kitanaka, Kazuya Shimoda
  • Organizer: 58th ASH Annual Meeting & Exposition
  • Place of Presentation: サンディエゴ（アメリカ合衆国）
  • Year and Date: 2016-12-03
  • Int'l Joint Research
• [Presentation] CALRdel52 mutation activates the JAK-STAT pathway in coordination with MPL, and causes ET in mice. (2016)
  • Author(s): Kotaro Shide, Takuro Kameda, Masaaki Sekine, Ayako Kamiunten, Keiichi Akizuki, Yuki Tahira, Haruko Shimoda, Tomonori Hidaka, Yoko Kubuki, Arata Honda, Akira Kitanaka, Kazuya Shimoda
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-10-15
• [Presentation] ＴＥＴ2欠損はHBZトランスジェニックマウスの病態を増悪させる (2016)
  • Author(s): 亀田拓郎、幣光太郎、関根雅明、山路卓巳、田平優貴、秋月渓一、上運天綾子、下田晴子、日髙智徳、久冨木庸子、北中明、下田和哉
  • Organizer: 第3回日本HTLV-1学会学術集会
  • Place of Presentation: 鹿児島県市町村自治会館（鹿児島市）
  • Year and Date: 2016-08-27
• [Presentation] Importance of bone marrow (BM) biopsy for diagnosing polycythemia vera (PV) in clinical practice (2015)
  • Author(s): Takuro Kameda，Kotaro Shide，Keiichi Akizuki，Masaaki Sekine，Ayako Kamiunten，Haruko Shimoda，Tomonori Hidaka， Yoko Kubuki，Akira Kitanaka，Kazuya Shimoda
  • Organizer: 第77回日本血液学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16
• [Book] 診断と治療のABC113 慢性骨髄背白血病 骨髄増殖性腫瘍 (2016)
  • Author(s): 亀田拓郎、下田和哉
  • Total Pages: 223
  • Publisher: 株式会社最新医学社
• [Book] 白血病学（下）－最新の基礎，臨床研究－ (2016)
  • Author(s): 亀田拓郎、下田和哉
  • Total Pages: 582
  • Publisher: 日本臨牀社
• [Book] Annual Review 血液 2016 (2016)
  • Author(s): 小野-宇留賀友佳子 松原由美子 石川文彦 大津 真 坂口大俊 加藤剛二 室井一男 高橋義行 臼杵憲祐 廣川 誠 原田結花 原田浩徳 張替秀郎 籠谷勇紀 亀田拓郎 幣 光太郎 他
  • Total Pages: 236
  • Publisher: 中外医学社