Interaction between NPM1 which is deeply related with the prognosisof leukemia and the ETS family of transcription factor, MEF

• Project/Area Number: 22591040
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Nagasaki University
• Principal Investigator: MIYAZAKI Yasushi 長崎大学, 大学院・医歯薬学総合研究科, 教授 (40304943)
• Co-Investigator(Renkei-kenkyūsha): ANDO Koji 長崎大学, 大学病院, 医員 (90571357)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 血液腫瘍学 / ETS遺伝子 / MEF / ELF4 / NPM1 / 急性骨髄性白血病 / 遺伝子変異 / 転写因子

Research Abstract

Myeloid ELF1-like factor (MEF), a member of the ETS transcription factors, can function as an oncogene. We found that MEF directly forms a complex with NPM1. Functional analyses showed that wild-type NPM1 inhibited the DNA-binding and transcriptional activity of MEF on the HDM2 promoter whereas NPM1 mutant protein (Mt-NPM1) enhanced these activities of MEF. It also related to the transformation of NIH3T3 cells by MEF. In addition, clinical leukemia samples with NPM1 mutations had higher HDM2 mRNA expression. Our data suggest that enhanced HDM2 expression induced by mutant NPM1 may have a role in MEF/ELF4-dependent leukemogenesis. (J Biol Chem 2013;288(13):9457-67.)

Research Products

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  • DOI: 10.1074/jbc.m112.415703
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• [Journal Article] Differences in the distribution of subtypes according to the WHO classification 2008 between Japanese and German patients with refractory anemia according to the FAB classification in myelodysplastic syndromes. (2010)
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• [Journal Article] Transplantation of allogeneic hematopoietic stem cells for adult T-cell leukemia : a nationwide retrospective study. (2010)
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• [Journal Article] Intensified consolidation therapy with dose-escalated doxorubicin did not improve the prognosis of adults with acute lymphoblastic leukemia : the JALSG-ALL97 study. (2010)
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• [Journal Article] Correlation Between Imatinib Pharmacokinetics and Clinical Response in Japanese Patients With Chronic-Phase Chronic Myeloid Leukemia. (2010)
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• [Journal Article] AMLに対する分子標的療法の現状と展望 (2010)
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• [Journal Article] I.白血病の分子標的療法 (2010)
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• [Journal Article] [第71回日本血液学会学術集会 シンポジウム1 標準リスク急性白血病第一寛解期の治療選択-移植vs化学療法の臨床決断のための思考過程-]急性骨髄性白血病の場合-JALSGの経験から- (2010)
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• [Journal Article] [第11回日本検査血液学会学術集会シンポジウム1 造血器腫瘍の改訂WHO2008分類の特徴と将来展望]2.AML/MDSの分類と新たな治療戦略 (2010)
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  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-21
• [Presentation] The usefulness of WT1 mRNA expression levels as a monitoring marker of MDS progression (2012)
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  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
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• [Presentation] IPSS-Rの改訂 (2012)
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  • Organizer: 第74回日本血液学会学術集会
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  • Year and Date: 2012-10-21
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  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2012-10-19
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  • Author(s): Yasushi Miyazaki, Koji Ando, Hideki Tsushima
  • Organizer: Interaction of ELF-4 and NPM1 in AML. :第10回日本臨床腫瘍学会学術集会
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  • Year and Date: 2012-07-27
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  • Organizer: The 3rd JSH International Symposium 2012 in Kawagoe
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  • Year and Date: 2012-05-26
• [Presentation] The 3rd JSH International Symposium 2012 in Kawagoe:Ve ry Long-term Follow-up Results of Tyrosine Kinase Inhibitor Therapy in Newly Diagnosed Chronic Myeloid Leukemia:Nagasaki CML Study Group Experience (2012)
  • Author(s): Hidehiro Itonaga, Tomoko Hata, Hideki Tsushima, Hiroaki Tanigucih, Junya Makiyama, Shinya Sato, Emi Matsuo, Reishi Yamasaki, Daisuke Ogawa, Yumi Takasaki, Daisuke Imanishi, Yoshitaka Imaizumi, Yasuhisa Kawaguchi, Tatsuro Joh, Shinichiro Yoshida, Masaomi Yamamura, Hisashi Soda, Yukiyoshi Moriuchi, Masao Tomonaga, Yasushi Miyazaki
  • Organizer: The 3rd JSH International Symposium 2012 in Kawagoe
  • Place of Presentation: 川越市(埼玉)
  • Year and Date: 2012-05-26
• [Presentation] Allogeneic StemCell Transplantation at the Primary Induction Failure or after the 1st Relapse Dose not Conquer Poor Prognosis of AML with FLT3-ITD (2012)
  • Author(s): Rika Kihara, Hitoshi Kiyoi, Shigeaki Ohtake, Shuichi Miyawaki, Yasushi Miyazaki, Norio Asou, Toru Sakura, Yukiyasu Ozawa, Noriko Usui, Heiwa Kanamori, Toru Kiguchi, Kiyotoshi Imai, Naokuni Uike, Fumihiro Kimura, Tomoki Naoe
  • Organizer: The 3rd JSH International Symposium 2012 in Kawagoe
  • Place of Presentation: 川越市(埼玉)
  • Year and Date: 2012-05-26
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  • Author(s): Tomohiko Taki, Hee-Je Kim, Shigeki Ohtake, Byung-Sik Cho, Hitoshi Kiyoi, Woo-Sung Min, Norio Asou, So-Young Choi, Yasushi Miyazaki, Yeo-Kyeoung Kim, Hisashi Sakamaki, June-Won Cheong, Sumihisa Honda, Shuichi Miyawaki, Masafumi Taniwaki, Hyeoung-Joon Kim, Tomoki Naoe, and Yoo-Hong Min
  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
• [Presentation] A Phase III Study of New Synthetic Retinoid Tamibarotene (Am80) Compared with ATRA in Maintenance Therapy for Newly Diagnosed Acute Promyelocytic Leukemia (APL): Japan Adult Leukemia Study Group (JALSG) APL204 Study (2012)
  • Author(s): Katsuji Shinagawa, Shigeki Ohtake, Toru Sakura, Yasunori Ueda, Masashi Sawa, Jun-ichi Miyatake, Noriko Usui, Makoto Onitsuka, Yoshihiro Hatta, Nobuhiko Emi, Shigehisa Tamaki, Yoshikazu Ito, Toru Murayama, Hiroyuki Fujita, Katsumichi Fujimaki, Norio Asou, Akihiro Takeshita, Yasushi Miyazaki, Shuichi Miyawaki, Kazunori Ohnishi, Tomoki Naoe, and Ryuzo Ohno
  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
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  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
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  • Author(s): Noriyoshi Iriyama, Yoshihiro Hatta, Jin Takeuchi, Yoshiaki Ogawa, Shigeki Ohtake, Toru Sakura, Kinuko Mitani, Fumihiro Ishida, Masatomo Takahashi, Tomoya Maeda, Tohru Izumi, Hisashi Sakamaki, Shuichi Miyawaki, Sumihisa Honda, Yasushi Miyazaki, Tomohiko Taki, Masafumi Taniwaki, and Tomoki Naoe
  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
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  • Author(s): Toru Sakura, Fumihiko Hayakawa, Toshiaki Yujiri, Yasutaka Aoyama, Eisei Kondo, Katsumichi Fujimaki, Yasunori Ueda, Shigeki Ohtake, Yasushi Miyazaki, Shuichi Miyawaki, Kazunori Ohnishi, and Tomoki Naoe
  • Organizer: 54th ASH Annual Meeting and Exposition
  • Place of Presentation: Atlanta, USA
• [Presentation] Interaction of ELF-4 and NPM1 in AML. (2012)
  • Author(s): Yasushi Miyazaki
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪市
  • Invited
• [Presentation] 左前腕部腫瘤を契機に診断された芽球性形質細胞様樹状細胞腫瘍の1例 (2011)
  • Author(s): 加藤丈晴, 牧山純也, 波多智子, 今西大介, 今泉芳孝, 田口潤, 塚崎邦弘, 宮崎泰司, 新野大介, 大島孝一
  • Organizer: 日本内科学会九州支部主催第295回九州地方会
  • Place of Presentation: 佐賀大学医学部臨床講堂
  • Year and Date: 2011-11-20
• [Presentation] Clinical significance of cytogenetic abnormalities in acute myeloid leukemia : the JALSG AML201 study (2011)
  • Author(s): Tomohiko Taki, Kazuhiro Nishida, Shigeki Ohtake, Yasushi Miyazaki, Jin Takeuchi, Ikuo Miura, Itsuro Jinnai, kazuma Ohyashiki, Hisashi Sakamaki, Shuichi Miyawaki, Sumihisa Honda, Kazunori Ohnishi, Ryuzo Ohno, Tomoki Naoe, Masafumi Taniwaki
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2011-10-15
• [Presentation] Transcriptional Activity of MEF/ELF4 on the HDM2 Promoter Is Enhanced by the Mutation of the NPM1 Gene. (2010)
  • Author(s): Ando Koji, Matsuo Emi, Horio Kensuke, Tominaga Shinya, Imanishi Daisuke, Imaizumi Yoshitaka, Tsushima Hideki, Iwanaga Masako, Kiyoi Hitoshi, Naoe Tomoki, Miyazaki Yasushi
  • Organizer: 52th American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: Orando, FL, Orange Country Convention Center USA
  • Year and Date: 2010-12-06
• [Presentation] ATL治療の進歩 (2010)
  • Author(s): 宮崎泰司
  • Organizer: 第42回日本内科学会九州支部主催教育講演会
  • Place of Presentation: 鹿児島大学医学部鶴陵会館(鹿児島県)
  • Year and Date: 2010-11-14
• [Presentation] 骨髄異形成症候群の分子標的治療 (2010)
  • Author(s): 宮崎泰司
  • Organizer: 第48回日本癌治療学会学術集会
  • Place of Presentation: 国立京都国際会館、グランドプリンスホテル京都(京都府)
  • Year and Date: 2010-10-30
• [Presentation] 36month follow-up of a phase I / II study of nilotinib for imatinib-resistant or -intolerant CML-CP. (2010)
  • Author(s): Kazuma Oyashiki, Kensuke Usuki, Arinobu Tojo, Yasuhiro Maeda, Tatsuya Kawaguchi, Akira Matsuda, Yukio Kobayashi, Koichi Miyamura, Akirou Kimura, Yasushi Miyazaki, Taro Amagasaki, Eiji kawahara, Aira Wanajo, Tomoki Naoe
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-26
• [Presentation] Clinical significance of WT1mRNA expression level in patients with myelodysplastic syndrome(MDS). (2010)
  • Author(s): Yasuhito Nannya, Mineo Kurokawa, Yasunori Ueda, Jin Takeuchi, Hideto Tamura, Kiyoyuki Ogata, Hirohiko Shibayama, Keiko Niimi, Nobuhiko Emi, Toshiko Motoji, KouSasaki, kensuke Usuki, Hiroyasu Ogawa, Toru Sakura, Kazuma Ohyashiki, Keiya Ozawa, Masaharu Kasai, Yasushi Miyazaki, Yasunobu Morita, Akira Matsuda, Kaoru Tohyama, Daisuke Koga, Hiroya Tamaki, Kinuko Mitani, Tomoki Naoe, Haruo Sugiyama, Fumimaro Takaku
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-26
• [Presentation] Mutation of IDH1 and IDH2 genes in cytogenetically normal acute myeloid leukemia. (2010)
  • Author(s): Hideaki Hoshino, Hitoshi Kiyoi, Syuuichi Miyawaki, Yasushi Miyazaki, Kazutaka Kuriyama, Masao Tomonaga, Tomoki Naoe
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-25
• [Presentation] Decision analysis of HLA-matched unrelated stem cell transplantation for ALL in first remission. (2010)
  • Author(s): Shinichi Kako, Satoshi Morita, Hisashi Sakamaki, Hiroatsu Iida, Mineo Kurokawa, Koichi Miyamura, Heiwa Kanamori, Masamichi Hara, Naoki Kobayashi, Yasuo Morishima, Keisei Kawa, Taichi Kyo, Toru Sakura, Itsuro Jinnai, Jin Takeuchi, Yasushi Miyazaki, Shuichi Miyawaki, Kazunori Ohnishi, Tomoki Naoe, Yoshinobu Kanda
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-25
• [Presentation] Coexistence of renal AL amyloidosis and gastrointestinal AA amyloidosis in multiple myeloma patient. (2010)
  • Author(s): Masataka Taguchi, Jun Taguchi, Daisuke Imanishi, Yoshitaka Imaizumi, Tomoko Hata, Takuya Fukushima, Kunihiro Tsukasaki, Yasushi Miyazaki
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-25
• [Presentation] Prognostic impact of blood transfusion dependency in lower risk MDS patients. (2010)
  • Author(s): Yoriko Inoue, Tomoko Hata, Jun Taguchi, Yoshitaka Imaizumi, Hideki Tsushima, Kazuhiro Nagai, Masao Tomonaga, Yasushi Miyazaki
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-25
• [Presentation] 急性骨髄性白血病の分子病態と診断 (2010)
  • Author(s): 宮崎泰司
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] The function of MEF is regulated by NPM1 that participate in leukemogenesis in AML. (2010)
  • Author(s): Koji Ando, Emi Matsuo, Shinya Tominaga, Kensuke Horio, Daisuke Imanishi, Yoshitaka Imaizumi, Hideki Tsushima, Hitoshi Kiyoi, Tomoki Naoe, Yasushi Miyazaki
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] Progressive metastatic pulmonary calcification associated with adult T-cell leukemia/lymphoma(ATL). (2010)
  • Author(s): Junya Makiyama, Jun Taguchi, Hidehiro Itonaga, Yoshitaka Imaizumi, Daisuke Imanishi, Takuya Fukushima, Tomoko Hata, Kunihiro Tsukasaki, Yasushi Miyazaki, Yuuji Ishimatsu, Tomayoshi Hayashi
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] BCR-ABL mutation status before and during nilotinib treatment in patients with CML and Ph+ALL. (2010)
  • Author(s): Arinobu Tojo, Kazuma Ohyashiki, Chiaki Nakaseko, Yasushi Miyazaki, Taro Amagasaki, Eiji Kawahara, Masamitsu Yanada, Tomoki Naoe
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-09-24
• [Presentation] 骨髄異形成症候群に対する診断と治療の現状 (2010)
  • Author(s): 宮崎泰司
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場・リーガロイヤルホテル大阪(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] AML/MDSの分類と新たな治療戦略 (2010)
  • Author(s): 宮崎泰司
  • Organizer: 第11回日本検査血液学会学術集会
  • Place of Presentation: 東京ビックサイト(東京都)
  • Year and Date: 2010-07-24
• [Book] EBM血液疾患の治療 (2012)
  • Author(s): 宮崎泰司
  • Total Pages: 3
  • Publisher: 中外医学社
• [Book] 新臨床腫瘍学（改訂第3版） (2012)
  • Author(s): 宮﨑泰司
  • Total Pages: 9
  • Publisher: 南江堂
• [Book] 白血病診療ポケットブック (2011)
  • Author(s): 宮崎泰司
  • Publisher: (株)中外医学社(東京)
• [Book] 血液専門医テキスト (2011)
  • Author(s): 宮崎泰司
  • Publisher: (株)南江堂(東京)
• [Book] 現場で役立つ血液腫瘍プロトコール集改訂版 (2011)
  • Author(s): 宮崎泰司
  • Publisher: (株)医薬ジャーナル社(大阪・東京)
• [Book] 平成23年度厚生労働科学研究がん臨床研究成果発表会(研究者向け)抄録集 (2011)
  • Author(s): 直江知樹, 薄井紀子, 大西一功, 竹内仁, 臼杵憲祐, 小林幸夫, 宮崎泰司, 熱田由子, 矢ヶ崎史治, 松村到
  • Publisher: 公益財団法人日本対がん協会がん臨床研究推進室
• [Book] Annual Review 血液2011 (2011)
  • Author(s): 宮崎泰司
  • Publisher: (株)中外医学社(東京)
• [Book] 血液疾患最新の治療 2011-2013 (2010)
  • Author(s): 宮崎泰司
  • Publisher: (株)南江堂(東京)