2018 Fiscal Year Annual Research Report
Molecular pathogenesis in myelodysplastic syndromes (MDS).
Project/Area Number |
26221308
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Research Institution | Kyoto University |
Principal Investigator |
小川 誠司 京都大学, 医学研究科, 教授 (60292900)
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Co-Investigator(Kenkyū-buntansha) |
古関 明彦 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (40225446)
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Project Period (FY) |
2014-05-30 – 2019-03-31
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Keywords | 血液内科学 / 血液腫瘍学 / 骨髄異形成症候群 |
Outline of Annual Research Achievements |
骨髄異形成症候群(MDS)およびその関連疾患は、骨髄不全と急性骨髄性白血病への進展を特徴とする、高齢者に好発する慢性骨髄性腫瘍である。MDSの主な死因である骨髄不全および急性白血病に関して、本研究課題において昨年度までに、全ゲノムおよびRNAシーケンスを含む世界トップレベルの遺伝子解析技術とマウスモデルを駆使した手法を用いて、多様な遺伝子変異がMDSを発症させ、MDSを白血病へ進展させるメカニズムについて明らかにした。本年度は、その成果に基づき、以上の解析結果を臨床情報と併せて解析することにより、予後を規定する遺伝子変異および発現異常の臨床的なインパクトを確認した。スプライス因子の変異に関しては、マウスモデルによる基礎的な機能解析を行い、変異マウスに特徴的なスプライス異常と、造血障害を確認した。さらに、コヘシン変異のマウスモデルに関しては、合併する変異とのマウスの交配を行い、詳細な機能解析を行った。その結果、コヘシン変異にRUNX1変異が合併することにより、コヘシン変異単独に比較して、DNAの三次元構造に著明な変化をみとめた。この三次元構造の変化は、付属するヒストン修飾蛋白の機能を変化させ、エピジェネティックな機序によりMDSから急性白血病への進展に関与する遺伝子発現に異常を起こし、臨床経過と関連することを明らかにした。この結果は学会発表をへて、現在論文化の予定である。このほか、最も予後が不良であることが知られているTP53変異陽性のMDSに関しても、その予後解析を詳細に行い、典型的な複雑核型をともなわないTP53変異陽性MDSの特徴について、国際共同研究を行い論文化し報告した。
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Research Progress Status |
平成30年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
平成30年度が最終年度であるため、記入しない。
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Research Products
(72 results)
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[Journal Article] Molecular pathogenesis of disease progression in MLL-rearranged AML2019
Author(s)
Kotani S, Yoda A, Kon A, Kataoka K, Ochi Y, Shiozawa Y, Hirsch C, Takeda J, Ueno H, Yoshizato T, Yoshida K, Nakagawa MM, Nannya Y, Kakiuchi N, Yamauchi T, Aoki K, Shiraishi Y, Miyano S, Maeda T, Maciejewski JP, Takaori-Kondo A, Ogawa S, Makishima H
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Journal Title
Leukemia
Volume: 33
Pages: 612-624
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Prominence of nestin-expressing Schwann cells in bone marrow of patients with myelodysplastic syndromes with severe fibrosis.2019
Author(s)
Suma S, Sakata-Yanagimoto M, Nguyen TB, Hattori K, Sato T, Noguchi M, Nannya Y, Ogawa S, Watanabe R, Fujimoto M, Nakamura N, Kusakabe M, Nishikii H, Kato T, Chiba S."
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Journal Title
Int J Hematol.
Volume: 109
Pages: 309-318
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pathogenic mutations identified by a multimodality approach in 117 Japanese Fanconi anemia patients.2019
Author(s)
Mori M, Hira A, Yoshida K, Muramatsu H, Okuno Y, Shiraishi Y, Anmae M, Yasuda J, Tadaka S, Kinoshita K, Osumi T, Noguchi Y, Adachi S, Kobayashi R, Kawabata H, Imai K, Morio T, Tamura K, Takaori-Kondo A, Yamamoto M, Miyano S, Kojima S, Ito E, Ogawa S, Matsuo K, Yabe H, Yabe M, Takata M.
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Journal Title
Haematologica.
Volume: -
Pages: -
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] KLF1 Mutation E325K Induces Cell-cycle Arrest in Erythroid Cells Differentiated from Congenital Dyserythropoietic Anemia (CDA) Patient-specific Induced Pluripotent Stem Cells.2019
Author(s)
Kohara H, Utsugisawa T, Sakamoto C, Hirose L, Ogawa Y, Ogura H, Sugawara A, Aoki T, Iwasaki T, Asai T, Doisaki S, Okuno Y, Muramatsu H, Abe T, Kurita R, Miyamoto S, Sakuma T, Shiba M, Yamamoto T, Ohga S, Yoshida K, Ogawa S, Ito E, Kojima S, Kanno H, Tani K.
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Journal Title
Exp Hematol.
Volume: 73
Pages: 25-37
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Japan Adult Leukemia Study G. Clinical significance of ASXL2 and ZBTB7A mutations and C-terminally truncated RUNX1-RUNX1T1 expression in AML patients with t(8;21) enrolled in the JALSG AML201 study.2019
Author(s)
Kawashima N, Akashi A, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kitamura K, Sakaida E, Takeshita A, Suzushima H, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H,
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Journal Title
Ann Hematol.
Volume: 98
Pages: 83-91.
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genomic landscape and clonal evolution of acute myeloid leukemia with t(8;21):2019
Author(s)
Christen F, Hoyer K, Yoshida K, Hou HA, Waldhueter N, Heuser M, Hills RK, Chan W, Hablesreiter R, Blau O, Ochi Y, Klement P, Chou WC, Blau IW, Tang JL, Zemojtel T, Shiraishi Y, Shiozawa Y, Thol F, Ganser A, Lowenberg B, Linch DC, Bullinger L, Valk PJM, Tien HF, Gale RE, Ogawa S, Damm F.
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Journal Title
Blood. .
Volume: 133
Pages: 1140-1151
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of enhancer of mRNA decapping 4 as a novel fusion partner of MLL in acute myeloid leukemia.2019
Author(s)
Becker H, Greve G, Kataoka K, Mallm JP, Duque-Afonso J, Ma T, Niemoller C, Pantic M, Duyster J, Cleary ML, Schuler J, Rippe K, Ogawa S, Lubbert M.
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Journal Title
Blood Adv.
Volume: 3
Pages: 761-765.
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Early detection and evolution of preleukemic clones in therapy-related myeloid neoplasms following autologous SCT2018
Author(s)
Berger G, Kroeze LI, Koorenhof-Scheele TN, de Graaf AO, Yoshida K, Ueno H, Shiraishi Y, Miyano S, van den Berg E, Schepers H, van der Reijden BA, Ogawa S, Vellenga E, Jansen JH
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Journal Title
Blood
Volume: 131
Pages: 1846-1857
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Infection perturbs Bach2- and Bach1-dependent erythroid lineage 'choice' to cause anemia.2018
Author(s)
Kato H, Itoh-Nakadai A, Matsumoto M, Ishii Y, Watanabe-Matsui M, Ikeda M, Ebina-Shibuya R, Sato Y, Kobayashi M, Nishizawa H, Suzuki K, Muto A, Fujiwara T, Nannya Y, Malcovati L, Cazzola M, Ogawa S, Harigae H, Igarashi K.
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Journal Title
Nat Immunol
Volume: 19
Pages: 1059-1070
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Germline loss of function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes.2018
Author(s)
Nagata Y, Narumi S, Guan Y, Przychodzen BP, Hirsch CM, Makishima H, Shima H, Aly M, Pastor V, Kuzmanovic T, Radivoyevitch T, Adema V, Awada H, Yoshida K, Li S, Sole F, Hanna R, Jha BK, LaFramboise T, Ogawa S, Sekeres MA, Wlodarski MW, Cammenga J, Maciejewski JP
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Journal Title
Blood
Volume: 132
Pages: 2309-2313
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia.2018
Author(s)
Shiozawa Y, Malcovati L, Gall? A, Sato-Otsubo A, Kataoka K, Sato Y, Watatani Y, Suzuki H, Yoshizato T, Yoshida K, Sanada M, Makishima H, Shiraishi Y, Chiba K, Hellstrom-Lindberg E, Miyano S, Ogawa S, Cazzola M
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Journal Title
Nat. Commun.
Volume: 9
Pages: 3649
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia.2018
Author(s)
Katagiri S, Umezu T, Azuma K, Asano M, Akahane D, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K
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Journal Title
Leuk Lymphoma
Volume: 59
Pages: 1490-1493
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is Reversed by IDH1/2-Mutant Inhibitors.2018
Author(s)
Molenaar RJ, Radivoyevitch T, Nagata Y, Khurshed M, Przychodzen B, Makishima H, Xu M, Bleeker FE, Wilmink JW, Carraway HE, Mukherjee S, Sekeres MA, van Noorden CJF, Maciejewski JP
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Journal Title
Clin Cancer Res
Volume: 24
Pages: 1705-1715
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clonally related diffuse large B-cell lymphoma and interdigitating dendritic cell sarcoma sharing MYC translocation.2018
Author(s)
Ochi Y, Hiramoto N, Yoshizato T, Ono Y, Takeda J, Shiozawa Y, Yoshida K, Kakiuchi N, Shiraishi Y, Tanaka H, Chiba K, Kazuma Y, Tabata S, Yonetani N, Uehara K, Yamashita D, Imai Y, Nagafuji K, Yamakawa M, Miyano S, Takaori-Kondo A, Ogawa S, Ishikawa T.
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Journal Title
Haematologica
Volume: 103
Pages: e553-e556
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] RUNX1 mutations in pediatric acute myeloid leukemia are associated with distinct genetic features and an inferior prognosis.2018
Author(s)
Yamato G, Shiba N, Yoshida K, Hara Y, Shiraishi Y, Ohki K, Okubo J, Park MJ, Sotomatsu M, Arakawa H, Kiyokawa N, Tomizawa D, Adachi S, Taga T, Horibe K, Miyano S, Ogawa S, Hayashi Y.
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Journal Title
Blood.
Volume: 131
Pages: 2266-2270.
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Germline loss of function SAMD9 and SAMD9L alterations in adult myelodysplastic syndromes.2018
Author(s)
Nagata Y, Narumi S, Guan Y, Przychodzen BP, Hirsch CM, Makishima H, Shima H, Aly M, Pastor V, Kuzmanovic T, Radivoyevitch T, Adema V, Awada H, Yoshida K, Li S, Sole F, Hanna R, Jha BK, LaFramboise T, Ogawa S, Sekeres MA, Wlodarski MW, Cammenga J, Maciejewski JP.
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Journal Title
Blood.
Volume: 6
Pages: 2309-2313
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Integrated molecular profiling of juvenile myelomonocytic leukemia.2018
Author(s)
Murakami N, Okuno Y, Yoshida K, Shiraishi Y, Nagae G, Suzuki K, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Ito M, Hirayama M, Watanabe A, Ueno T, Kojima S, Aburatani H, Mano H, Miyano S, Ogawa S, Takahashi Y, Muramatsu H.
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Journal Title
Blood.
Volume: 131
Pages: 1576-1586
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Evolutionary basis of HLA-DPB1 alleles affects acute GVHD in unrelated donor stem cell transplantation.2018
Author(s)
Morishima S, Shiina T, Suzuki S, Ogawa S, Sato-Otsubo A, Kashiwase K, Azuma F, Yabe T, Satake M, Kato S, Kodera Y, Sasazuki T, Morishima Y, Japan Marrow Donor P.
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Journal Title
Blood.
Volume: 131
Pages: 808-817
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Immune-Mediated Hematopoietic Failure after Allogeneic Hematopoietic Stem Cell Transplantation: A Common Cause of Late Graft Failure in Patients with Complete Donor Chimerism.2018
Author(s)
Maruyama K, Aotsuka N, Kumano Y, Sato N, Kawashima N, Onda Y, Maruyama H, Katagiri T, Zaimoku Y, Nakagawa N, Hosomichi K, Ogawa S, Nakao S.
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Journal Title
Biol Blood Marrow Transplant.
Volume: 24
Pages: 43-49
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid expansion.2018
Author(s)
Madan V, Han L, Hattori N, Teoh WW, Mayakonda A, Sun QY, Ding LW, Binte Mohd Nordin H, Lim SL, Shyamsunder P, Dakle P, Sundaresan J, Doan NB, Sanada M, Sato-Otsubo A, Meggendorfer M, Yang H, Said JW, Ogawa S, Haferlach T, Liang DC, Shih LY, Nakamaki T, Wang QT, Koeffler HP.
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Journal Title
Haematologica.
Volume: 103
Pages: 1980-1990
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Sudden Intracranial Hemorrhage in a Patient With Atypical Chronic Myeloid Leukemia in Chronic Phase.2018
Author(s)
Kouzuki K, Umeda K, Saida S, Kato I, Hiramatsu H, Funaki T, Kanda K, Muramatsu H, Yoshida K, Ogawa S, Adachi S.
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Journal Title
J Pediatr Hematol Oncol.
Volume: 40
Pages: e553-e556
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Infection perturbs Bach2- and Bach1-dependent erythroid lineage 'choice' to cause anemia.2018
Author(s)
Kato H, Itoh-Nakadai A, Matsumoto M, Ishii Y, Watanabe-Matsui M, Ikeda M, Ebina-Shibuya R, Sato Y, Kobayashi M, Nishizawa H, Suzuki K, Muto A, Fujiwara T, Nannya Y, Malcovati L, Cazzola M, Ogawa S, Harigae H, Igarashi K.
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Journal Title
Nat Immunol.
Volume: 19
Pages: 1059-1070
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia.2018
Author(s)
Katagiri S, Umezu T, Azuma K, Asano M, Akahane D, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K.
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Journal Title
Leuk Lymphoma.
Volume: 59
Pages: 1490-1493
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Distinct gene alterations with a high percentage of myeloperoxidase-positive leukemic blasts in de novo acute myeloid leukemia.2018
Author(s)
Kamijo R, Itonaga H, Kihara R, Nagata Y, Hata T, Asou N, Ohtake S, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Naoe T, Kiyoi H, Miyazaki Y.
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Journal Title
Leuk Res.
Volume: 65
Pages: 34-41.
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Donor cell-derived transient abnormal myelopoiesis as a specific complication of umbilical cord blood transplantation.2018
Author(s)
Hiramoto N, Takeda J, Yoshida K, Ono Y, Yoshioka S, Yamauchi N, Fujimoto A, Maruoka H, Shiraishi Y, Tanaka H, Chiba K, Imai Y, Miyano S, Ogawa S, Ishikawa T.
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Journal Title
Bone Marrow Transplant.
Volume: 53
Pages: 225-227.
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Japan Adult Leukemia Study Group J. Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study.2018
Author(s)
Harada Y, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kobayashi S, Kitamura K, Sakaida E, Onizuka M, Takeshita A, Ishida F, Suzushima H, Ishizawa K, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H,
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Journal Title
Leuk Res.
Volume: 66
Pages: 20-27
Peer Reviewed / Int'l Joint Research
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[Journal Article] Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.2018
Author(s)
Hamada M, Doisaki S, Okuno Y, Muramatsu H, Hama A, Kawashima N, Narita A, Nishio N, Yoshida K, Kanno H, Manabe A, Taga T, Takahashi Y, Miyano S, Ogawa S, Kojima S.
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Journal Title
Int J Hematol.
Volume: 108
Pages: 306-311
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gain-of-function IKBKB mutation causes human combined immune deficiency.2018
Author(s)
Cardinez C, Miraghazadeh B, Tanita K, da Silva E, Hoshino A, Okada S, Chand R, Asano T, Tsumura M, Yoshida K, Ohnishi H, Kato Z, Yamazaki M, Okuno Y, Miyano S, Kojima S, Ogawa S, Andrews TD, Field MA, Burgio G, Morio T, Vinuesa CG, Kanegane H, Cook MC.
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Journal Title
J Exp Med.
Volume: 215
Pages: 2715-2724
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Early detection and evolution of preleukemic clones in therapy-related myeloid neoplasms following autologous SCT.2018
Author(s)
Berger G, Kroeze LI, Koorenhof-Scheele TN, de Graaf AO, Yoshida K, Ueno H, Shiraishi Y, Miyano S, van den Berg E, Schepers H, van der Reijden BA, Ogawa S, Vellenga E, Jansen JH.
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Journal Title
Blood.
Volume: 131
Pages: 1846-1857
Peer Reviewed
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[Journal Article] Hematopoietic lineage distribution and evolutionary dynamics of clonal hematopoiesis.2018
Author(s)
Arends CM, Galan-Sousa J, Hoyer K, Chan W, Jager M, Yoshida K, Seemann R, Noerenberg D, Waldhueter N, Fleischer-Notter H, Christen F, Schmitt CA, Dorken B, Pelzer U, Sinn M, Zemojtel T, Ogawa S, Mardian S, Schreiber A, Kunitz A, Kruger U, Bullinger L, Mylonas E, Frick M, Damm F.
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Journal Title
Leukemia.
Volume: 131
Pages: 1846-1857
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Stag2 regulates hematopoietic differentiation and self-renewal2018
Author(s)
Yotaro Ochi, Ayana Kon, Masahiro Marshall Nakagawa, Keisuke Kataoka, Kenichi Yoshida, Haruhiko Koseki, Manabu Nakayama, Akinori Yoda, Hideki Makishima, Akifumi Takaori-Kondo2, and Seishi Ogawa
Organizer
23rd Congress of European Hematology Association (EHA)
Int'l Joint Research
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[Presentation] Comprehensive analysis for genetic factors predictive of azacitidine treatment for MDS.2018
Author(s)
Yasuhito Nannya, June Takeda, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Akifumi Takaori, Shigeru Chiba, Kazuma Ohyashiki, Yasushi Miyazaki, Tomoki Naoe, Satoru Miyano, Seishi Ogawa
Organizer
77th Anulal Meeeting of the Japanese Cancer Association
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[Presentation] Mechanisms of the clonal evolution of MDS as revealed by single-cell sequencing.2018
Author(s)
Masahiro M Nakagawa, Ryosaku Inagaki, Yasuhito Nannya, Zhao Lanying, June Takeda, Akinori Yoda, Ayana Kon, Tetsuichi Yoshizato, Hisashi Tsurumi, Hideki Makishima, and Seishi Ogawa
Organizer
第80回日本血液学会学術総会
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[Presentation] Analysis of clonal evolution/heterogeneity of MDS by simultaneous detection of both mutation and gene expression by single cell sequencing2018
Author(s)
Masahiro Marshall Nakagawa, Ryosaku Inagaki, Yasuhito Nannya, Lanying Zhao, Yutaka Kuroda, June Takeda, Xingxing Qi, Akinori Yoda, Ayana Kon, Hisashi Tsurumi, Hideki Makishima, Shuichi Matsuda and Seishi Ogawa
Organizer
60th American Society of Hematology Annual Meeting
Int'l Joint Research
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[Presentation] Clonal evolution of non-malignant proliferative lesions into breast cancers2018
Author(s)
Tomomi Nishimura, Kenichi Yoshida, Yukiko Kawata, Yasuhide Takeuchi, Nobuyuki Kakiuchi, Yusuke Shiozawa, Kosuke Aoki, Masahiro Hirata, Tatsuki R. Kataoka, Takaki Sakurai, Satoko Baba, Yuichi Shiraishi, Kenichi Chiba, Kengo Takeuchi, Hironori Haga, Satoru Miyano, Masakazu Toi, Seishi Ogawa
Organizer
San Antonio Breast Cancer Symposium 2018
Int'l Joint Research
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