In vivo analysis of gene mutations related to epigenetic alterations in acute myeloid leukemia
| Project/Area Number |
24591411
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ANDO Kiyoshi 東海大学, 医学部, 教授 (70176014)
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| Co-Investigator(Renkei-kenkyūsha) |
YAHATA Takashi 東海大学, 医学部, 講師 (10398753)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 急性骨髄性白血病 / epigenetics / 遺伝子変異 / ヒトCD34陽性細胞 / 臍帯血由来CD34陽性細胞 / PML-RARA / FLT3-ITD / DNMT3A / NPM1 / 臍帯血由来CD34陽性細 / NOGマウス / in vivoモデル |
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| Outline of Final Research Achievements |
This study aimed to see the in vivo function of genetic mutations that are related to the epigenetic alterations in acute myeloid leukemia (AML). We focused on the DNMT3A R882H mutation among them. Human CD34+ cells transduced with DNMT3A R882H reduced the expression of myelomonocytic markers such as CD14 and the formation of CFU-mix and CFU-GM in the colony formation assays. However, these cells could not develop AML in NOG mice when they were transplanted. Taken together, these findings suggest that the transduction of DNMT3A R882H was not enough for the development of AML in vivo.
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Report
(4 results)
Research Products
(61 results)
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[Journal Article] Establishment of a humanized APL model via the transplantation of PML-RARA-transduced human common myeloid progenitors into immunodeficient mice2014
Author(s)
Matsushita, H. Yahata, T. Sheng, Y. Nakamura, Y. Muguruma, Y. Matsuzawa, H. Tanaka, M. Hayashi, H. Sato, T. Damdinsuren, A. Onizuka, M. Ito, M. Miyachi, H. Pandolfi, P. P. Ando, K.
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Journal Title
PLoS One
Volume: 9
Issue: 11
Pages: e111082-e111082
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Functional analysis of the SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia.2014
Author(s)
Kawai H, Matsushita H, Suzuki R, Sheng Y, Lu J, Matsuzawa H, Yahata T, Tsuma-Kaneko M, Tsukamoto H, Kawada H, Ogawa Y, Ando K.
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Journal Title
Leukemia Research.
Volume: 38
Issue: 12
Pages: 1451-1559
DOI
Related Report
Peer Reviewed
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[Journal Article] Acute myeloid leukaemia with myelodysplastic features in children2014
Author(s)
Kinoshita A, Miyachi H, Matsushita H, Yabe M, Taki T, Watanabe T, Saito AM, Tomizawa D, Taga T, Takahashi H, Matsuo H, Kodama K, Ohki K, Hayashi Y, Tawa A, Horibe K, Adachi S.
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Journal Title
Br J Haematol
Volume: 167
Issue: 1
Pages: 80-86
DOI
Related Report
Peer Reviewed
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[Journal Article] RUNX1/AML1 mutant collaborates with BMI1 overexpression in the development of human and murine myelodysplastic syndromes.2013
Author(s)
Harada Y, Inoue D, Ding Y, Imagawa J, Doki N, Matsui H, Yahata T, Matsushita H, Ando K, Sashida G, Iwama A, Kitamura T, Harada H.
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Journal Title
Related Report
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[Presentation] In vivo analysis of PML-RARA in a humanized mouse model2014
Author(s)
Matsushita H, Yahata T, Sheng Y, Nakamura Y, Muguruma Y, Matsuzawa H, Tanaka M, Hayashi H, Sato T, Damdinsuren A, Onizuka M, Ito M, Miyachi H, Pandolfi PP, Ando K
Organizer
56th ASH Annual Meeting & Exposition
Place of Presentation
San Francisco, CA, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] Sufficient reduction of anthracycline doses in the treatment of childhood acute promyelocytic leukemia: A nationwide prospective study by the Japanese Pediatric Leukemia / Lymphoma Study Group (JPLSG)2014
Author(s)
akahashi H, Watanabe T, Kinoshita A, Yuza Y, Moritake H, Terui K, Iwamoto S, Nakayama H, Shimada A, Kudo K, Taki T, Yabe M, Matsushita H, Yamashita Y, Koike K, Ogawa A, Kosaka Y, Tomizawa D, Taga T, Saito A, Horibe K, Nakahata T, Miyachi H, Tawa A, Adachi ST
Organizer
56th ASH Annual Meeting & Exposition
Place of Presentation
San Francisco, CA, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] Bone marrow adipocyte-derived free fatty acids induce gene signature linking transcription with metabolic changes that contribute to survival of acute monocytic leukemia cells2014
Author(s)
Tabe Y, Harada M, Miyamae Y, Mogushi K, Kazuno S, Fujimura T, Matsushita H, Ueno T, Yokomizo T, Miida T, Samudio I, Andreeff M, Konopleva M
Organizer
56th ASH Annual Meeting & Exposition
Place of Presentation
San Francisco, CA, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] The mTOR kinase inhibitior AZD-2014 effectively reverses XPO1/CRM1 antagonist KPT-185-induced glycolysis / gluconeogenesis, enhancing antitumor effects in mantle cell lymphoma2014
Author(s)
Tabe Y, Harada M, Miyamae Y, Matsushita H, Kojima K, Fujimura T, Kazuno S, Ueno T, Miida T, Konopleva M, Andreeff M
Organizer
56th ASH Annual Meeting & Exposition
Place of Presentation
san Francisco, CA, USA
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] The prognostic relevance of the 2008 WHO classification of myeloid neoplasms in childhood acute myeloid leukemia2014
Author(s)
Kinoshita A, Miyachi H, Matsushita H, Yabe M, Taki T, Watanabe T, Saito AM, Tomizawa D, Taga T, Takahashi H, Matsuo H, Kodama K, Ohki K, Hayashi Y, Tawa A, Horibe K, Adachi S
Organizer
19th Congress of European Hematology Association
Place of Presentation
Milan, Italy
Year and Date
2014-06-12 – 2014-06-15
Related Report
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[Presentation] A diversity of cases in AML with promyleocytic differentiation; A report from JPLSG2013
Author(s)
Takahashi H, Matsushita H, Kinoshita A, Taki T, Deguchi T, Kiyokawa N, Hashii Y, Hayashi Y, Tomizawa D, Taga T, Tawa A, Adachi S, Yabe M, Miyachi H
Organizer
第７５回 日本血液学会学術集会
Place of Presentation
ロイトン札幌、札幌市
Related Report
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[Presentation] Chemotherapy prior to HSCT is beneficial for pediatric RAEB/RAEB-T2013
Author(s)
Shimada A, Kinoshita A, Manabe A, Miyachi H, Matsushita H, Taki T, Inoue M, Hasegawa D, Hama A, Ito M, Tawa A, Kojima S, Adachi S
Organizer
第７５回 日本血液学会学術集会
Place of Presentation
ロイトン札幌、札幌市
Related Report
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[Presentation] Functional analysis of SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia2013
Author(s)
Kawai H, Matsushita H, Suzuki R, Sheng Y, Lu J, Yahata T, Matsuzawa H, Tsukamoto H, Kawada H, Ogawa Y, Ando K
Organizer
第７５回 日本血液学会学術集会
Place of Presentation
ロイトン札幌、札幌市
Related Report
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[Presentation] Integrative genomic and proteomic analysis of low-dose ionizing irradiation effects on bone marrow stromal microenvironment and on survival of pre-leukemic cells2013
Author(s)
Tabe Y, Jin L, Hatanaka Y, Matsushita H, Kazuno S, Fujimura T, Ueno T, Sasai K, Iwabuchi K, Andreeff M, Konopleva M, Miida T
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Functional analysis of SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia2013
Author(s)
Kawai H, Matsushita H, Suzuki R, Sheng Y, Lu J, Matsuzawa H, Yahata T, Kaneko M, Tsukamoto H, Kawada H, Ogawa Y, Ando K
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Molecular mechanisms of inhibition of ribosomal biogenesis and translational flux by the selective inhibitor of nuclear export (SINE) XPO1/CRM1 antagonist KPT-185 In mantle cell lymphoma2013
Author(s)
Tabe Y, Kojima K, Jin L, Iwanami H, Matsushita H, Kazuno S, Fujimura T, Ueno T, Miida T, Andreeff M
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Efficacy and mechanisms of the mTOR inhibitor AZD2014 combined with L-asparaginase or JAK2 inhibitor TG101348 In ALL2013
Author(s)
Tabe Y, Jin L, Iwanami H, Matsushita H, ,Kazuno S, Fujimura T, Ueno T, Miida T, Weinstock DM, Thomas DA, Andreeff M, Konopleva M
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Molecular mechanisms of adipocyte-leukemia interactions revealed by the quantitative proteomics technology: pro-survival function of adipocyte-derived free fatty acids on acute monoblastic leukemia mitochondrial biogenesis2013
Author(s)
Tabe Y, Jin L, Kazuno S, Fujimura T, Matsushita H, Ueno T, Miida T, Andreeff, M, Konopleva
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Metabolic shift in hypoxia-adapted CML cells and mechanisms of acquired dasatinib resistance uncovered by proteomic iTRAQ profiling2013
Author(s)
Tabe Y, Jin L, Iwanami H, Matsushita H, Kazuno S, Fujimura T, Ueno T, MiidaT, Andreeff M, Konopleva M, Kimura S
Organizer
55th ASH Annual Meeting and Exposition
Place of Presentation
Ernest N. Morial Convention Center, New Orleans, LA
Related Report
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[Presentation] Humanized in vivo APL model using human cord blood initiate by induction of PML-RARA.2012
Author(s)
Matsushita H, Yahata T, Nakamura Y, Sheng Y, Muguruma Y, Matsuzawa H, Uno T, Takanashi T, Satou T, Tanaka M, Hayashi H, Miyachi H, Ando K
Organizer
The 3rd JSH International Symposium 2012 in Kawagoe
Place of Presentation
埼玉県川越市
Related Report
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[Presentation] unctional analysis of SEPT9-ABL1 chimeric fusion gene derived from T-prolymphocytic leukemia.2012
Author(s)
Matsushita H, Suzuki R, Sheng Y, Yahata T, Matsuzawa H, Tsukamoto H, Kawai H, Kawada H, Ogawa Y, Miyachi H, Ando K
Organizer
第74回 日本血液学会学術集会
Place of Presentation
京都府京都市
Related Report
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[Presentation] Myelodysplasia-Related Changes Have Adverse Prognostic Significance in Children with Acute Myeloid Leukemia; A Report From the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).2012
Author(s)
Kinoshita A, Miyachi H, Matsushita H, Yabe M, Taki T, Watanabe T, Saito A, Tomizawa D, Kiyokawa N,Taga T, Deguchi T, Hayashi Y, Terui K, Takahashi H, Hayashi Y, Tawa A, Horibe K, Adachi S
Organizer
The 54th American Society of Hematology Annual Meeting
Place of Presentation
Atlanta, GA
Related Report
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[Presentation] Analysis of Dasatinib-Induced Molecular Mechanisms of Apoptosis in Hypoxia-Adopted CML Cells Utilizing Quantitative Proteomics Technology.2012
Author(s)
Tabe Y, Jin L, Iwanami H, Kazuno S, Fujimura T, Matsushita H, Ueno T, Miida T, Andreeff M, Konopleva M, Kimura S
Organizer
The 54th American Society of Hematology Annual Meeting
Place of Presentation
Atlanta, GA
Related Report
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