Development of an epoch-making method for identification of Down syndrome patients with TAM who will subsequently develop acute megakaryoblastic leukemia
Project/Area Number |
15K15384
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Pediatrics
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Research Institution | Hirosaki University |
Principal Investigator |
Ito Etsuro 弘前大学, 医学研究科, 教授 (20168339)
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Co-Investigator(Kenkyū-buntansha) |
土岐 力 弘前大学, 医学研究科, 講師 (50195731)
照井 君典 弘前大学, 医学研究科, 准教授 (00333740)
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Project Period (FY) |
2015-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | TAM / Down症候群 / 急性巨核芽球性白血病 / GATA1 / 小児白血病 / ダウン症候群 / MRD / ダウン症 |
Outline of Final Research Achievements |
The goal of this study is to develop an epoch-making method for identification of Down syndrome patients with transient abnormal myelopoiesis (TAM) who will subsequently develop acute megakaryoblastic leukemia (DS-AMKL) and establish the base for developing the prophylaxis for DS-AMKL. The results of this study are as follows. All patients with TAM and DS-AMKL have GATA1 mutations. To detect minimal residual diseases (MRD) of TAM, we developed highly sensitive methods to detect GATA1 mutations (sensitivity 0.02%) using target next-generation sequencing. We next performed whole exome sequencing of 40 sets of samples from DS-AMKL patients at diagnosis of AMKL and remission phases, and identified several novel mutational targets, which will be useful as MRD markers.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.2016
Author(s)
Shiba N, Yoshida K, Shiraishi Y, Okuno Y, Yamato G, Hara Y, Nagata Y, Chiba K, Tanaka H, Terui K, Kato M, Park MJ, Ohki K, Shimada A, Takita J, Tomizawa D, Kudo K, Arakawa H, Adachi S, Taga T, Tawa A, Ito E, Horibe K, Sanada M, Miyano S, Ogawa S, Hayashi Y.
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Journal Title
Br J Haematol.
Volume: 175
Issue: 3
Pages: 476-489
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Systematic cellular disease models reveal synergistic interactions of trisomy 21 and GATA1 mutations in hematopoietic abnormalities2016
Author(s)
K. Banno, S. Omori, K. Hirata, N. Nawa, N. Nakagawa, K. Nishimura, M. Ohtaka, M. Nakanishi, T. Sakuma, T. Yamamoto, T. Toki, E. Ito, T. Yamamoto, C. Kokubu, J. Takeda, H. Taniguchi, H. Arahori, K. Wada, Y. Kitabatake and K. Ozono
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Journal Title
Cell Reports
Volume: 15
Issue: 6
Pages: 1-15
DOI
NAID
Related Report
Peer Reviewed / Open Access
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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
Author(s)
Taga T, Watanabe T, Tomizawa D, Kudo K, Kiminori Terui K, Moritake H, Kinoshita A, Iwamoto S, Nakayama H, Takahashi H, Shimada A MD, Taki T, Toki T, Ito E, Goto H, Koh K, Saito AM, Horibe K, Nakahata T, Tawa A, Adachi S.
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Journal Title
Pediatr Blood Cancer
Volume: 63
Issue: 2
Pages: 248-54
DOI
Related Report
Peer Reviewed
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[Journal Article] Transient myeloproliferative disorder with partial trisomy 21.2015
Author(s)
Takahashi T, Inoue A, Yoshimoto J, Kanamitsu K, Taki T, Imada M, Yamada M, Ninomiya S, Toki T, Terui K, Ito E, Shimada A.
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Journal Title
Pediatr Blood Cancer
Volume: 62
Issue: 11
Pages: 2021-2024
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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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 Yanagisawa, 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
Related Report
Int'l Joint Research / Invited
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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
Int'l Joint Research / Invited
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[Presentation] DNA methylation state correlates with progression of myeloid leukemia in Down syndrome.2015
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
Int'l Joint Research
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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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