Novel therapeutic approaches for treatment of myeloproliferative neoplasms based on aging control
Project/Area Number |
18K08358
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Yamaguchi University |
Principal Investigator |
Yujiri Toshiaki 山口大学, 大学院医学系研究科, 教授 (80346551)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 骨髄増殖性腫瘍 / 細胞老化 |
Outline of Final Research Achievements |
Myeloproliferative neoplasms (MPN) are often characterized by specific somatic mutations: JAK2, CALR, or MPL. A single nucleotide polymorphism (SNP), rs2736100, in the reverse transcriptase gene (TERT) and a germline JAK2 46/1 haplotype(46/1) have been associated with MPN in North American and European patients. We examined 201 Japanese MPN patients, as well as 366 control individuals for TERT rs2736100 and JAK2 rs10974944, a tagging SNP of the 46/1. Correlations between the JAK2 V617F allele burden and TERT rs2736100 or JAK2 rs10974944 were evaluated using a digital PCR assay. The 46/1, but not the TERT rs2736100, was correlated to the JAK2 V617F mutant allele burden in JAK2 V617F-positive MPN patients. In conclusion, we demonstrated that both TERT rs2736100_C and 46/1 are predisposing factors for MPNs in Japanese patients. While TERT rs2736100_C tended to have a more general, non-specific effect on all MPNs, the 46/1 was essentially predisposed to the JAK2 V617F-positive MPNs.
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Academic Significance and Societal Importance of the Research Achievements |
骨髄増殖性腫瘍は高齢者によく認められる疾患である。一般的には経過の緩徐な疾患であるが、脳心血管疾患リスクは高くなり生活の質が低下する。さらに二次性骨髄線維症や急性骨髄性白血病への病勢進行に加え、他の固形癌の発症も問題になる。今回の我々の研究では遺伝的背景(TERT遺伝子多型)に起因する骨髄増殖性腫瘍に加え、他の固形癌のリスク因子となるが日本人患者でも明らかになった。今後、高齢患者の増加に伴い重複癌患者の増加が推測されていることから重要な情報となる事が考えられる。また血管リスク因子を遺伝的背景から同定することができれば、さらに有用な情報となり得る。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Optimal treatment strategy with nilotinib for patients with newly diagnosed chronic-phase chronic myeloid leukemia based on early achievement of deep molecular response (MR 4.5 ): The phase 2, multicenter N-Road study2020
Author(s)
Kaichi Nishiwaki, Kei-Ji Sugimoto, Shigehisa Tamaki, Junichi Hisatake, Hisayuki Yokoyama, Tadahiko Igarashi, Atsushi Shinagawa, Takeaki Sugawara, Satoru Hara, Kazuhisa Fujikawa, Seiichi Shimizu, Toshiaki Yujiri, Arinobu Tojo, Hisashi Wakita
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Journal Title
Cancer Med .
Volume: 9
Pages: 3742-3751
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Case of Pulmonary Langerhans Cell Histiocytosis With Acute Progressive Nodular Lesions Depicted on High-Resolution Computed Tomography.2019
Author(s)
Kunihiro Y, Hara A,, Ikeda E, Nakada N, Murakami T, Hayashi M, Okabe K, Yujiri T, Kamei H, Tanaka N, Onoda H, Matsumoto T, Ito K
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Journal Title
J Thorac Imaging.
Volume: 34
DOI
Related Report
Peer Reviewed
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[Journal Article] Significance of Granulocyte Colony-Stimulating Factor-Combined High-Dose Cytarabine, Cyclophosphamide, and Total Body Irradiation in Allogeneic Hematopoietic Cell Transplantation for Myeloid Malignant Neoplasms.2019
Author(s)
Nakamura Y, Tanaka Y, Tanaka M, Yamamoto K, Matsuguma M, Kajimura Y, Tokunaga Y, Yujiri T, Tanizawa Y
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Journal Title
Transplant Proc.
Volume: 51
Pages: 896-900
DOI
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Peer Reviewed
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[Journal Article] Bortezomib-based strategy with autologous stem cell transplantation for newly diagnosed multiple myeloma: a phase II study by the Japan Study Group for Cell Therapy and Transplantation (JSCT-MM12).2019
Author(s)
Sunami K, Matsumoto M, Fuchida SI, Omoto E, Takamatsu H, Adachi Y, Choi I, Fujishima N, Kiguchi T, Miyamoto T, Maeda A, Suzumiya J, Yamamura R, Nagafuji K, Nakazato T, Kuroda Y, Yujiri T, Takamatsu Y, Harada M, Akashi K
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Journal Title
Int J Clin Oncol.
Volume: 24
Pages: 966-975
DOI
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Peer Reviewed
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[Journal Article] Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL2018
Author(s)
Hatta Y, Mizuta S, Matsuo K, Ohtake S, Iwanaga M, Sugiura I, Doki N, Kanamori H, Ueda Y, Yoshida C, Dobashi N, Maeda T, Yujiri T, Monma F, Ito Y, Hayakawa F, Takeuchi J, Kiyoi H, Miyazaki Y, Naoe T
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Journal Title
Ann Hematol.
Volume: 97
Pages: 1535-1545
DOI
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Peer Reviewed / Open Access
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[Journal Article] A distinct subtype of Epstein Barr virus positive T/NK-cell lymphoproliferative disorder: Adult patients with chronic active Epstein Barr virus infection-like features.2018
Author(s)
Kawamoto K, Miyoshi H, Suzuki T, Kozai Y, Kato K, Miyahara M, Yujiri T, Choi I, Fujimaki K, Muta T, Kume M, Moriguchi S, Tamura S, Kato T, Tagawa H, Makiyama J, Kanisawa Y, Sasaki Y, Kurita D, Yamada K, Shimono J, Sone H, Takizawa J, Seto M, Kimura H, Ohshima K.
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Journal Title
Haematologica
Volume: Epub
Pages: 1018-1028
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] CD34 E-Scoreは自家末梢血幹細胞採取成否の予測モデルとなる2020
Author(s)
山本 薫, 中邑 幸伸, 重本 航輝, 田中 芳紀, 田中 真由美, 佐々木 貴宏, 徳永 良洋, 梶邑 泰子, 松隈 雅史, 湯尻 俊昭, 谷澤 幸生
Organizer
第82回日本血液学会学術集会
Related Report
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[Presentation] 未治療多発性骨髄腫に対する自家造血幹細胞移植の第2相試験(JSCT-MM14)2020
Author(s)
角南 一貴, 長藤 宏司, 上村 智彦, 宮本 敏浩, 松本 守生, 小川 亮介, 村田 了一, 瀧澤 淳, 松村 到, 大本 英次郎, 半田 寛, 湯尻 俊昭, 富永 亮, 高松 博幸, 日高 道弘, 杉田 純一, 藤島 直仁, 淵田 真一, 高松 泰, 原田 実根, 赤司 浩一
Organizer
第82回日本血液学会学術集会
Related Report
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