The multistep molecular mechanism of acute megakaryoblastic leukemia in Down syndrome
Project/Area Number |
26253061
|
Research Category |
Grant-in-Aid for Scientific Research (A)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Pediatrics
|
Research Institution | Hirosaki University |
Principal Investigator |
Ito Etsuro 弘前大学, 医学研究科, 教授 (20168339)
|
Co-Investigator(Kenkyū-buntansha) |
照井 君典 弘前大学, 医学研究科, 准教授 (00333740)
土岐 力 弘前大学, 医学研究科, 講師 (50195731)
金崎 里香 弘前大学, 医学研究科, 助教 (60722882)
|
Project Period (FY) |
2014-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥41,080,000 (Direct Cost: ¥31,600,000、Indirect Cost: ¥9,480,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2016: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
Fiscal Year 2015: ¥11,050,000 (Direct Cost: ¥8,500,000、Indirect Cost: ¥2,550,000)
Fiscal Year 2014: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
|
Keywords | 白血病 / ダウン症候群 / TAM / 急性巨核芽球性白血病 / GATA1 / コヒーシン / CTCF / EZH2 / ダウン症 |
Outline of Final Research Achievements |
We performed functional study of Down syndrome associated acute megakaryocytic leukemia (DS-AMKL)-specific mutations to understand the mechanisms of multistep leukemogenesis in DS, and found the following results. 1)We found many novel recurrent mutations in DS-AMKL samples using whole exome sequencing, and performed functional study for these mutations. 2)We established the K562 subclones expressing GATA1s exclusively (GATA1s subclones) using CRISPR/Cas9 gene editing. GATA1s subclones expressed KIT at higher levels compared to the wild type K562. Engineered DNA-binding molecule-mediated ChIP (enChIP) sequencing and 3C-based proximity ligation assays revealed that in the GATA1s subclone, GATA1-binding region at -87 kb with respect to the transcription start site was more proximate to the KIT transcriptional start site compared to the wild type, suggesting that the N-terminal domain of GATA1 is essential for proper genomic conformation and gene expression regulation of KIT.
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Report
(5 results)
Research Products
(45 results)
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Br J Haematol.
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[Journal Article] Erythrocyte glutathione is a novel biomarker of Diamond-Blackfan anemia2016
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Utsugisawa T, Uchiyama T, Toki T, Ogura H, Aoki T, Hamaguchi I, Ishiguro A, Ohara A, Kojima S, Ohga S, Ito E, Kanno H
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[Journal Article] The phenotype and clinical course of Japanese Fanconi Anaemia infants is influenced by patient, but not maternal ALDH2 genotype.2016
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Br J Haematol.
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Cell Reports
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[Journal Article] Preserved High Probability of Overall Survival with Significant Reduction of Chemotherapy for Myeloid Leukemia in Down Syndrome: A Nationwide Prospective Study in Japan.2016
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[Journal Article] ALDH2 polymorphism in patients with Diamond-Blackfan anemia in Japan.2016
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Leukemia.
Volume: 8
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[Presentation] Integrated genetic/epigenetic analysis revealed high heterogeneity of acute lymphoblastic leukemia in Down syndrome2017
Author(s)
Yasuo Kubota, Kumiko Uryu, Tatsuya Ito, Tomoko Kawai, Masafumi Seki, Tomoya Isobe, Tsutomu Toki, Kenichi Yoshida, Keisuke Kataok), Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Akira Oka, Yasuhide Hayashi, Seishi Ogawa, Kiminori Terui, Atsuhi Sato, Kenichiro Hata, Etsuro Ito, Junko Takita
Organizer
59th ASH Annual Meeting and Exposition
Related Report
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[Presentation] Clinical impact of GATA1 mutation types in infants with Down syndrome and TAM: JPLSG TAM-10 study.2017
Author(s)
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Organizer
第79回日本血液学会学術集会
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[Presentation] 8.Clinical sequencing of 375 patients with inherited and acquired bone marrow failure syndromes2017
Author(s)
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Organizer
EWOG-S/SAA2017
Related Report
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[Presentation] Analysis of GATA1 mutations in Down syndrome infants with transient abnormal myelopoiesis and clinical impacts of GATA1 mutation types: A report from the JPLSG TAM-10 study.2016
Author(s)
Kiminori Terui, Tsutomu Toki, Asahito Hama, Hideki Muramatsu, Daisuke Hasegawa, Myoung-ja Park, Shotaro Iwamoto, Takashi Taga, Ryu Yanagisawa7, Katsuyoshi Koh, Akiko M. Saito, Keizo Horibe, Yasuhide Hayashi, Souichi Adachi, Shuki Mizutani, Kenichiro Watanabe and Etsuro Ito
Organizer
American Society of Hematology 58th Annual Meeting
Place of Presentation
SanDiego, CA, USA
Year and Date
2016-12-03
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[Presentation] Gene expression profiles and methylation analysis in Down syndrome related acute lymphoblastic leukemia2016
Author(s)
Yasuo Kubota, Kumiko Uryu, Tomoko Kawai, Tatsuya Ito, Isamu Hanada, Tsutomu Toki, Masafumi Seki, Kenichi Yoshida, Yusuke Sato, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Akira Oka, Yasuhide Hayashi, Seishi Ogawa, Kiminori Teru), Atsushi Sato, Kenichiro Hata, Etsuro Ito, Junko Takita
Organizer
American Society of Hematology 58th Annual Meeting
Place of Presentation
SanDiego, CA, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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[Presentation] Genetic and Epigenetic Alterations in Acute Megakaryoblastic Leukemia in Down Syndrome.2016
Author(s)
Etsuro Ito, Kenichi Yoshida, Tsutomu Toki, Satoshi Saida, Kenichiro Watanabe, Masahiro Nakamura, Kiminori, Terui, Tatsutoshi Nakahata, Satoru Miyano, Akira Watanabe, Seishi Ogawa
Organizer
Fifth JCA-AACR Special Joint Conference -The Latest Advances in Hematological Cancer Research: From Basic Science to Therapeutics.
Place of Presentation
Tokyo Bay Maihama Hotel, Urayasu, Chiba
Year and Date
2016-07-13
Related Report
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[Presentation] DNA methylation state correlates with progression of myeloid leukemia in Down syndrome2015
Author(s)
Saida S, Nakamura M, Toki T, Arai Y, Terui K, Yoshida Y, Ogawa S, Nakahata T, Heike T, Watanabe K, Watanabe A, Ito E
Organizer
第57回アメリカ血液学会
Place of Presentation
オーランド(米国)
Year and Date
2015-12-05
Related Report
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[Presentation] Prospective study of 168 infants with transient abnormal myelopoiesis with Down syndrome: Japan Pediatric Leukemia/Lymphoma Study Group, TAM-10 study2015
Author(s)
Muramatsu H, Watanabe T, Hasegawa D, Park M, Iwamoto S, Taga T, Ito E, Toki T, Terui K, Yanagisawa R, Koh K, Saito A, Horibe K, Hayashi Y, Adachi S, Mizutani S, Watanabe K
Organizer
第57回アメリカ血液学会
Place of Presentation
オーランド(米国)
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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