Molecular pathogenesis of bone marrow failure elucidated by comprehensive sequencing.

• Project/Area Number: 16H05338
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto University
• Principal Investigator: MAKISHIMA HIDEKI 京都大学, 医学研究科, 准教授 (40402127)
• Research Collaborator: YOSHIDA Kenichi ; KON Ayana ; KATAOKA Keisuke ; ONO Kinji ; KOSEKI Haruhiko ; Miyazaki Yasushi ; Chiba Shigeru ; Nakao Shinji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000); Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
• Keywords: 骨髄不全症候群 / 再生不良性貧血 / 発作性夜間血色素尿症 / 骨髄異形成症候群 / 遺伝子変異 / コピー数異常 / 遺伝子発現異常 / 二次性白血病 / ゲノム異常 / 血液内科 / タイプ1変異 / タイプ2変異 / ゲノム / 内科 / 遺伝子 / 臨床

Outline of Final Research Achievements

In this study, we clarified novel pathogenesis of bone marrow hypoplasia and luekemia evolustion in cases with bone marrow failure syndromes by simultaneous genome and transcriptome analysis.
Genomic and RNA sequencing in the same case revealed that novel mutations, copy number alterations, and abnormal gene expression were significantly associated with pathophysiology of bone marrow failure syndromes. For example, gene expression and its associated mutations defined new classification of bone marrow failures into different groups such as stem cell and erythroid phenoytpes, which were related to clinical course of leukemia evolution. In addition, novel SAMD9/SAMD9L mutations and chromosome 7 deletions were coincidently identified in secondary myelodysplastic syndromes after congenital bone marrow failure. These findings were validated by analysis using basic animal models and clinical information on prognosis and morphological phenotype.

Academic Significance and Societal Importance of the Research Achievements

骨髄不全症候群は、骨髄異形成症候群、再生不良性貧血、発作性夜間血色素尿症を含む、骨髄造血機能の障害を共通の病態とする難治性疾患である。これらの疾患は、共通の遺伝子異常を呈しながらも、疾患特異的な異常をも来たすことが明らかとなっていた。これらの研究成果を踏まえ、本研究では、骨髄不全症候群おいてどのような異常がゲノム上あるいは遺伝子発現パターンに起こり、より悪性度の高い難治性の病型に変化するのか、さらに白血病への変化を引き起こすのかについて、これまでに培ったシーケンス技術と、マウスモデルを用いた機能解析によって明らかにした。

Research Products

• [Int'l Joint Research] Cleveland Clinic./Case Western Reserve University.(米国)
• [Int'l Joint Research] Munich Leukemia Laboratory./University of Freiburg.(ドイツ)
• [Int'l Joint Research] University of Pavia.(イタリア)
• [Int'l Joint Research] University of Amsterdam.(オランダ)
• [Int'l Joint Research] King Chulalongkorn Memorial Hospital.(タイ)
• [Int'l Joint Research]
• [Int'l Joint Research] Cleveland Clinic/NIH(米国)
• [Int'l Joint Research] MLL(Germany)
• [Int'l Joint Research] Pavia University(Italy)
• [Int'l Joint Research] University of Amsterdam(Netherlands)
• [Int'l Joint Research] Chang Gung University(台湾)
• [Int'l Joint Research]
• [Int'l Joint Research] Cleveland Clinic/NIH/Albert Einstein College of Medicine(米国)
• [Int'l Joint Research] MLL/University Hospital Essen(Germany)
• [Int'l Joint Research] Pavia University(Italy)
• [Int'l Joint Research] Radboud University/University of Amsterdam(Netherlands)
• [Int'l Joint Research] Chang Gung University(台湾)
• [Int'l Joint Research]
• [Journal Article] Frequent germline mutations of HAVCR2 in sporadic subcutaneous panniculitis-like T-cell lymphoma (2019)
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  • Journal Title: Blood Advances Volume: 3 Issue: 4 Pages: 588-595
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  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas (2019)
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  • Journal Title: Leukemia Volume: Epub ahead of print Issue: 7 Pages: 1687-1699
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• [Journal Article] Age-related remodelling of oesophageal epithelia by mutated cancer drivers. (2019)
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  • Journal Title: Nature Volume: 565 Issue: 7739 Pages: 312-317
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• [Journal Article] Molecular pathogenesis of disease progression in MLL-rearranged AML. (2018)
  • 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.
  • Journal Title: Leukemia Volume: 33 Issue: 3 Pages: 612-624
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• [Journal Article] Clonal hematopoiesis in aplastic anemia (2018)
  • Author(s): Makishima H.
  • Journal Title: Rinsho Ketsueki Volume: 59 Issue: 10 Pages: 1962-1968
  • DOI: 10.11406/rinketsu.59.1962
  • NAID: 130007496730
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  • Peer Reviewed
• [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
  • Journal Title: Blood Volume: 132 Issue: 21 Pages: 2309-2313
  • DOI: 10.1182/blood-2017-05-787390
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Journal Title: Nat. Commun. Volume: 9 Issue: 1 Pages: 3649-3649
  • DOI: 10.1038/s41467-018-06063-x
  • NAID: 120006537149
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clonal PIGA mosaicism and dynamics in paroxysmal nocturnal hemoglobinuria. (2018)
  • Author(s): Clemente MJ, Przychodzen B, Hirsch CM, Nagata Y, Bat T, Wlodarski MW, Radivoyevitch T, Makishima H, Maciejewski JP
  • Journal Title: Leukemia Volume: 32 Issue: 11 Pages: 2507-2511
  • DOI: 10.1038/s41375-018-0138-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Journal Title: Clin Cancer Res Volume: 24 Issue: 7 Pages: 1705-1715
  • DOI: 10.1158/1078-0432.ccr-17-2796
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A novel genetic and morphologic phenotype of ARID2-mediated myelodysplasia (2018)
  • Author(s): Sakai H, Hosono N, Nakazawa H, Przychodzen B, Polprasert C, Carraway HE, Sekeres MA, Radivoyevitch T, Yoshida K, Sanada M, Yoshizato T, Kataoka K, Nakagawa MM, Ueno H, Nannya Y, Kon A, Shiozawa Y, Takeda J, Shiraishi Y, Chiba K, Miyano S, Singh J, Padgett RA, Ogawa S, Maciejewski JP, Makishima H
  • Journal Title: Leukemia Volume: 32(3) Issue: 3 Pages: 839-843
  • DOI: 10.1038/leu.2017.319
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fanconi Anemia germline variants as susceptibility factors in aplastic anemia, MDS and AML (2017)
  • Author(s): Przychodzen Bartlomiej、Makishima Hideki、Sekeres Mikkael A.、Balasubramanian Suresh Kumar、Thota Swapna、Patel Bhumika J.、Clemente Michael、Hirsch Cassandra、Dienes Brittney、Maciejewski Jaroslaw P.
  • Journal Title: Oncotarget Volume: 9 Issue: 2 Pages: 2050-2057
  • DOI: 10.18632/oncotarget.23328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Gene expression and risk of leukemic transformation in myelodysplasia (2017)
  • Author(s): Shiozawa Y, Malcovati L, Galli A, Pellagatti A, Karimi M, Sato-Otsubo A, Sato Y, Suzuki H, Yoshizato T, Yoshida K, Shiraishi Y, Chiba K, Makishima H, Boultwood J, Hellstroem-Lindberg E, Miyano S, Cazzola M, Ogawa S
  • Journal Title: Blood Volume: 130(24) Issue: 24 Pages: 2642-2653
  • DOI: 10.1182/blood-2017-05-783050
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sequential acquisition of mutations in myelodysplastic syndromes (2017)
  • Author(s): 牧島 秀樹
  • Journal Title: Rinsho Ketsueki Volume: 58 Issue: 10 Pages: 1828-1837
  • DOI: 10.11406/rinketsu.58.1828
  • NAID: 130006132649
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Hidden FLT3-D835Y clone in FLT3-ITD-positive acute myeloid leukemia that evolved into very late relapse with T-lymphoblastic leukemia (2017)
  • Author(s): Katagiri S, Umezu T, Asano M, Akahane D, Azuma K, Makishima H, Yoshida K, Watatani Y, Chiba K, Miyano S, Ogawa S, Ohyashiki JH, Ohyashiki K
  • Journal Title: Leukemia and Lymphoma Volume: 3 Issue: 6 Pages: 1-4
  • DOI: 10.1080/10428194.2017.1382696
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Origins of myelodysplastic syndromes after aplastic anemia. (2017)
  • Author(s): Negoro E., Nagata Y., Clemente MJ., Hosono N., Shen W., Nazha A., Yoshizato T., Hirsch C., Przychodzen B., Mahfouz RZ., Kuzmanovic T., Sekeres MA., Makishima H., Ogawa S., Maciejewski JP.
  • Journal Title: Blood Volume: 130 Issue: 17 Pages: 1953-1957
  • DOI: 10.1182/blood-2017-02-767731
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GATA4 loss of function in liver cancer impedes precursor to hepatocyte transition (2017)
  • Author(s): Enane Francis O.、Shuen Wai Ho、Gu Xiaorong、Quteba Ebrahem、Przychodzen Bartlomiej、Makishima Hideki、Bodo Juraj、Ng Joanna、Chee Chit Lai、Ba Rebecca、Seng Koh Lip、Lim Janice、Cheong Rachael、Teo Marissa、Hu Zhenbo、Ng Kwok Peng、Maciejewski Jaroslaw、Radivoyevitch Tomas、Chung Alexander、et al.
  • Journal Title: Journal of Clinical Investigation Volume: 127 Issue: 9 Pages: 3527-3542
  • DOI: 10.1172/jci93488
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genomic determinants of chronic myelomonocytic leukemia (2017)
  • Author(s): Patel B. J., Przychodzen B., Thota S., Radivoyevitch T., Visconte V., Kuzmanovic T., Clemente M., Hirsch C., Morawski A., Souaid R., Saygin C., Nazha A., Demarest B., LaFramboise T., Sakaguchi H., Kojima S., Carraway H. E., Ogawa S., Makishima H., Sekeres M. A., Maciejewski J. P.
  • Journal Title: Leukemia Volume: 31 Issue: 12 Pages: 2815-2823
  • DOI: 10.1038/leu.2017.164
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Somatic SETBP1 mutations in myeloid neoplasms (2017)
  • Author(s): Makishima Hideki
  • Journal Title: International Journal of Hematology Volume: 105 Issue: 6 Pages: 732-742
  • DOI: 10.1007/s12185-017-2241-1
  • Peer Reviewed
• [Journal Article] Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells. (2017)
  • Author(s): Pan F, Wingo TS, Zhao Z, Gao R, Makishima H, Qu G, Lin L, Yu M, Ortega JR, Wang J, Nazha A, Chen L, Yao B, Liu C, Chen S, Weeks O, Ni H, Phillips BL, Huang S, Wang J, He C, Li GM, Radivoyevitch T, Aifantis I, Maciejewski JP, Yang FC, Jin P, Xu M.
  • Journal Title: Nat Commun. Volume: 8 Issue: 1 Pages: 15102-15102
  • DOI: 10.1038/ncomms15102
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] ynamics of clonal evolution in myelodysplastic syndromes. (2017)
  • Author(s): Makishima H, et al.
  • Journal Title: Nat Genet. Volume: 49 Issue: 2 Pages: 204-212
  • DOI: 10.1038/ng.3742
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Molecular features of early onset adult myelodysplastic syndrome. (2017)
  • Author(s): Hirsch CM, Przychodzen BP, Radivoyevitch T, Patel B, Thota S, Clemente MJ, Nagata Y, LaFramboise T, Carraway H, Nazha A, Sekeres MA, Makishima H, Maciejewski JP.
  • Journal Title: Haematologica. Volume: 印刷中 Issue: 6 Pages: 1028-1034
  • DOI: 10.3324/haematol.2016.159772
  • NAID: 120006360781
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A myeloid tumor suppressor role for NOL3. (2017)
  • Author(s): Stanley RF, Piszczatowski RT, Bartholdy B, Mitchell K, McKimpson WM, Narayanagari S, Walter D, Todorova TI, Hirsch C, Makishima H, Will B, McMahon C, Gritsman K, Maciejewski JP, Kitsis RN, Steidl U.
  • Journal Title: J Exp Med. Volume: 214 Issue: 3 Pages: 753-771
  • DOI: 10.1084/jem.20162089
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of genetic alterations in stem-cell transplantation for myelodysplasia and secondary acute myeloid leukemia. (2017)
  • Author(s): Yoshizato T, et. al., Sanada M, et. al., Ogawa S.
  • Journal Title: Blood Volume: 129 Issue: 17 Pages: 2347-2358
  • DOI: 10.1182/blood-2016-12-754796
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Deletion of Ptpn1 induces myeloproliferative neoplasm. (2017)
  • Author(s): Jobe F, Patel B, Kuzmanovic T, Makishima H, Yang Y, Przychodzen B, Hutchison RE, Bence KK, Maciejewski JP, Mohi G.
  • Journal Title: Leukemia. Volume: 印刷中 Issue: 5 Pages: 1229-1234
  • DOI: 10.1038/leu.2017.31
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recurrent genetic defects on chromosome 5q in myeloid neoplasms. (2017)
  • Author(s): Hosono N, Makishima H, Mahfouz R, Przychodzen B, Yoshida K, Jerez A, LaFramboise T, Polprasert C, Clemente MJ, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Sanada M, Cui E, Verma AK, McDevitt MA, List AF, Saunthararajah Y, Sekeres MA, Boultwood J, Ogawa S, Maciejewski JP.
  • Journal Title: Oncotarget. Volume: 8 Issue: 4 Pages: 6483-6495
  • DOI: 10.18632/oncotarget.14130
  • NAID: 120006355735
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Gene mutations in myelodysplastic syndromes (2016)
  • Author(s): Makishima H, Ogawa S.
  • Journal Title: Rinsho Ketsueki Volume: 57 Issue: 12 Pages: 2543-2553
  • DOI: 10.11406/rinketsu.57.2543
  • NAID: 130005286788
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Gene mutations in bone marrow failure syndromes (2016)
  • Author(s): Yoshizato T, Makishima H.
  • Journal Title: Rinsho Ketsueki Volume: 57 Issue: 12 Pages: 2519-2525
  • DOI: 10.11406/rinketsu.57.2519
  • NAID: 130005286796
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Somatic PHF6 mutations in 1760 cases with various myeloid neoplasms. (2016)
  • Author(s): Mori T, Nagata Y, Makishima H, Sanada M, Shiozawa Y, Kon A, Yoshizato T, Sato-Otsubo A, Kataoka K, Shiraishi Y, Chiba K, Tanaka H, Ishiyama K, Miyawaki S, Mori H, Nakamaki T, Kihara R, Kiyoi H, Koeffler HP, Shih LY, Miyano S, Naoe T, Haferlach C, Kern W, Haferlach T, Ogawa S, Yoshida K.
  • Journal Title: Leukemia. Volume: 30 Issue: 11 Pages: 2270-2273
  • DOI: 10.1038/leu.2016.212
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Somatic mosaicism in chronic myeloid leukemia in remission. (2016)
  • Author(s): Mitani K, Nagata Y, Sasaki K, Yoshida K, Chiba K, Tanaka H, Shiraishi Y, Miyano S, Makishima H, Nakamura Y, Nakamura Y, Ichikawa M, Ogawa S.
  • Journal Title: Blood. Volume: 128 Pages: 2863-2866
  • Peer Reviewed
• [Journal Article] Molecular predictors of response in patients with myeloid neoplasms treated with lenalidomide. (2016)
  • Author(s): Negoro E, Radivoyevitch T, Polprasert C, Adema V, Hosono N, Makishima H, Przychodzen B, Hirsch C, Clemente MJ, Nazha A, Santini V, McGraw KL, List AF, Sole F, Sekeres MA, Maciejewski JP.
  • Journal Title: Leukemia. Volume: 30 Issue: 12 Pages: 2405-2409
  • DOI: 10.1038/leu.2016.228
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epigenetic therapy as a novel approach for GFI136N-associated murine/human AML. (2016)
  • Author(s): Botezatu L, Michel LC, Helness A, Vadnais C, Makishima H, Hones JM, Robert F, Vassen L, Thivakaran A, Al-Matary Y, Lams RF, Schutte J, Giebel B, Gorgens A, Heuser M, Medyouf H, Maciejewski J, Duhrsen U, Moroy T, Khandanpour C.
  • Journal Title: Exp Hematol. Volume: 44 Issue: 8 Pages: 713-726
  • DOI: 10.1016/j.exphem.2016.05.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GFI1(36N) as a therapeutic and prognostic marker for myelodysplastic syndrome. (2016)
  • Author(s): Botezatu L, Michel LC, Makishima H et al.
  • Journal Title: Exp Hematol. Volume: 44 Issue: 7 Pages: 590-595
  • DOI: 10.1016/j.exphem.2016.04.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GFI1 as a novel prognostic and therapeutic factor for AML/MDS. (2016)
  • Author(s): Hones JM et al.,Hergenhan SM, Thivakaran A, Schutte J, Al-Matary YS, Lams RF, Fraszscak J, Makishima H et al.
  • Journal Title: Leukemia. Volume: 30 Issue: 6 Pages: 1237-1245
  • DOI: 10.1038/leu.2016.11
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations. (2016)
  • Author(s): Hamilton BK, Visconte V, Jia X, Tabarroki A, Makishima H, Hasrouni E, Abounader D, Kalaycio M, Sekeres MA, Sobecks R, Duong Liu H, Bolwell B, Maciejewski JP, Copelan E, Tiu RV.
  • Journal Title: Am J Hematol. Volume: 91 Issue: 4 Pages: 406-409
  • DOI: 10.1002/ajh.24306
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 再生不良性貧血とクローン性造血 (2018)
  • Author(s): 牧島秀樹
  • Organizer: 日本血液学会総会
  • Invited
• [Presentation] Somatic and Germline Mutations in Myelodysplastic Syndromes. (2018)
  • Author(s): Hideki Makishima
  • Organizer: The 6th TSH International Symposium.
  • Int'l Joint Research / Invited
• [Presentation] Sequential acquisition of mutations in myelodysplastic syndromes. (2018)
  • Author(s): Hideki Makishima
  • Organizer: 41st IRCMS Seminar.
  • Int'l Joint Research / Invited
• [Presentation] Sequential acquisition of genetic mutations in myelodysplastic syndromes (MDS). (2018)
  • Author(s): Hideki Makishima
  • Organizer: Annual Colloquium (Cancer Course, Kyoto University)
  • Invited
• [Presentation] MOLECULAR PATHOGENESIS OF DISEASE PROGRESSION IN MLLREARRANGED AML. (2018)
  • Author(s): Shinichi Kotani, Keisuke Kataoka, Akinori Yoda, Ayana Kon, et al., Akifumi Takaori-Kondo, Seishi Ogawa, Hideki Makishima.
  • Organizer: 23rd Congress of European Hematology Association (EHA)
  • Int'l Joint Research
• [Presentation] Invariant Patterns of Clonal Succession Determines Specific Phenotypic and Clinical Features of Myelodysplastic Syndromes (MDS). (2018)
  • Author(s): Yasunobu Nagata, Hideki Makishima et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Novel and Significant Impact of Germline Variants Predisposed to Pathogenic Somatic Mutations and Loss of Heterozygosity (LOH) in Myelodysplastic Syndromes (MDS) and Clonal Hematopoiesis of Indeterminate Potential (CHIP). (2018)
  • Author(s): Hideki Makishima et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Opposing Pathogenesis of Germline SAMD9/SAMD9L Variants in Adult Myelodysplastic Syndrome (MDS). (2018)
  • Author(s): Yasunobu Nagata, Satoshi Narumi, Yihong Guan, Bartlomiej Przychodzen, Cassandra Hirsch, Hideki Makishima et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Genomic Analysis of Myelodysplastic Syndromes Among Nagasaki Atomic Bomb Survivors. (2018)
  • Author(s): Masataka Taguchi et al., Hideki Makishima, Yasuhito Nannya, Yukiyoshi Moriuchi, Seishi Ogawa, Koh-ichiro Yoshiura, Yasushi Miyazaki.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Modulation of TET2 Activity By Ascorbic Acid and Factors Affecting Lysine Acetylation. (2018)
  • Author(s): Yihong Guan et al., Hideki Makishima, Aziz Nazha, Daniel Gackowski, Ewelina Zarakowska, Mridul Mukherji, Mikkael Sekeres, Mingjiang Xu, Ryszard linski, Jaroslaw Maciejewsk, Babal Jha.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Pan-Myeloid Leukemia Analysis: Machine Learning-Based Approach to Predict Phenotype and Clinical Outcomes Using Mutation Data. (2018)
  • Author(s): Kiyomi Morita, Feng Wang, Hideki Makishima et al.
  • Organizer: 60th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] 正常造血細胞への遺伝子異常の蓄積と急性骨髄性白血病発症機序 (2018)
  • Author(s): 牧島秀樹
  • Organizer: 第16回 日本再生医療学会総会
  • Invited
• [Presentation] Clonal hematopoiesis in aplastic anemia.-CLONAL DYNAMICS ESCAPING FROM AUTOIMMUNITY- (2017)
  • Author(s): Hideki Makishima
  • Organizer: Korean Society of Hematology
  • Int'l Joint Research / Invited
• [Presentation] A novel genetic and morphologic phenotype of ARID2-mediated myelodysplastic syndromes. (2017)
  • Author(s): Hitoshi Sakai , Naoko Hosono , Hideyuki Nakazawa , Bartlomiej Przychodzen , Chantana Polprasert , Hetty Carraway , Mikkael Sekeres , Tomas Radivoyevitch , et al., Seishi Ogawa , Jaroslaw Maciejewski , Hideki Makishima
  • Organizer: 22nd Congress of European Hematology Association
  • Int'l Joint Research
• [Presentation] Transcriptome Sequencing Reveals Distinct Subtypes of Myelodysplasia with Prognostic Significance. (2017)
  • Author(s): Yusuke Shiozawa, Luca Malcovati, Anna Galli, Andrea Pellagatti, Mohsen Karimi, Aiko Sato-Otsubo, Yusuke Sato, Hiromichi Suzuki, Tetsuichi Yoshizato, Kenichi Yoshida, Yuichi Shiraishi, Kenichi Chiba, Hideki Makishima, Jacqueline Boultwood, Eva Hellstrom Lindberg, Satoru Miyano, Mario Cazzola, Seishi Ogawa
  • Organizer: 22nd Congress of European Hematology Association
  • Int'l Joint Research
• [Presentation] Advancement of Molecular Pathogenesis in Myelodysplastic Syndromes (2017)
  • Author(s): Hideki Makishima
  • Organizer: Hematology Meeting, University of Freiburg
  • Int'l Joint Research / Invited
• [Presentation] Comprehensive Evaluation of DDX41 Risk Alleles in Non-Familial Cases, General Individuals, and Donor-Derived Leukemias (2017)
  • Author(s): Hideki Makishima
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Functional and Biological Implications of CUX1 Mutations and Deletions in Myeloid Neoplasms (2017)
  • Author(s): Mai Aly, Zubaidah M Ramdzan, Yasunobu Nagata, Suresh K. Balasubramanian, Naoko Hosono, Hideki Makishima, Valeria Visconte, Bartlomiej P. Przychodzen, Cassandra M. Hirsch, Mikkael A. Sekeres, Alain Nepveu, and Jaroslaw Maciejewski
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Molecular Pathogenesis of Progressive Refractoriness in MLL -Rearranged AML. (2017)
  • Author(s): Shinichi Kotani, Keisuke Kataoka, June Takeda, Hiroo Ueno, Yusuke Shiozawa, Tetsuichi Yoshizato, Ayana Kon, Kenichi Yoshida, Yasuhito Nannya, Akinori Yoda, Yuichi Shiraishi, Satoru Miyano, Akifumi Takaori-Kondo, Hideki Makishima and Seishi Ogawa
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] IDH1/2-Mutated Acute Myeloid Leukemia Has Impaired DNA Damage Response and Is Sensitive to Monotherapy with the PARP Inhibitior Olaparib. (2017)
  • Author(s): Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata,Bartlomiej P. Przychodzen, Hideki Makishima, Hetty E. Carraway, Sudipto Mukherjee, Mikkael A. Sekeres, Cornelis van Noorden, and Jaroslaw P. Maciejewski
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] Non-Random Interactions between Founder and Subclonal Mutations Shape the Clinical and Morphological Features of MDS (2017)
  • Author(s): Yasunobu Nagata, Hideki Makishima, Cassandra M. Hirsch, Mai Aly, Abhinav Goyal, Hassan Awada, Mohammad Fahad B Asad, Teodora Kuzmanovic, Bartlomiej P. Przychodzen et al., Mikkael A. Sekeres, Torsten Haferlach, Seishi Ogawa, and Jaroslaw P. Maciejewski
  • Organizer: The 59th American Society of Hematology Annual Meeting
  • Int'l Joint Research
• [Presentation] 骨髄異形成症候群の分子病態 ー遺伝子変異の経時的な獲得ー (2017)
  • Author(s): 牧島秀樹
  • Organizer: 第15回 日本臨床腫瘍学会学術集会
  • Invited
• [Presentation] Precision medicine for early detection of clonal evolution in myelodysplastic syndromes (2017)
  • Author(s): Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Yasuhito Nannya, Yasunobu Nagata, Yusuke Okuno, Yuichi Shiraishi, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Torsten Haferlach, Jaroslaw P. Maciejewski, Seishi Ogawa
  • Organizer: 第76回 日本癌学会学術総会
• [Presentation] MLL/AF9 急性骨髄性白血病における治療不応性に関わる網羅的遺 伝子解析 (2017)
  • Author(s): 小谷 槙一、片岡 圭亮、竹田 淳恵、上野 浩生、塩澤 裕介、吉里 哲一、昆 彩奈、吉田 健一、南谷 泰仁、依田 成玄、高折晃史、小川 誠司、牧島 秀樹
  • Organizer: 第76回 日本癌学会学術総会
• [Presentation] 骨髄異形成症候群におけるゲノム異常の段階的獲得 (2017)
  • Author(s): 牧島秀樹
  • Organizer: 第79回 日本血液学会学術集会
  • Invited
• [Presentation] MLL/AF9 急性骨髄性白血病における治療不応性に関わる網羅的遺 伝子解析 (2017)
  • Author(s): 小谷 槙一、片岡 圭亮、竹田 淳恵、上野 浩生、塩澤 裕介、吉里 哲一、昆 彩奈、吉田 健一、南谷 泰仁、依田 成玄、高折晃史、小川 誠司、牧島 秀樹
  • Organizer: 第79回 日本血液学会学術集会
• [Presentation] 骨髄異形成症候群（MDS）における、胚細胞および体細胞変異 ー遺伝子変異の経時的な獲得ー (2017)
  • Author(s): 牧島秀樹
  • Organizer: 日本人類遺伝学会総会 第62回大会
  • Invited
• [Presentation] 骨髄異形成症候群（MDS）における ゲノム異常の獲得パターンとその臨床的意義 (2017)
  • Author(s): 牧島秀樹
  • Organizer: 千里ライフサイエンスセミナー L4
  • Invited
• [Presentation] Clonal dynamics in myelodysplastic syndromes. (2016)
  • Author(s): Hideki Makishima.
  • Organizer: 5th International Conference on Myelodysplastic Syndromes, European School of Hematology.
  • Place of Presentation: Estoril, Portugal.
  • Int'l Joint Research / Invited
• [Presentation] MDS genomics and its clinical implication. (2016)
  • Author(s): Hideki Makishima.
  • Organizer: The Fifth National Conference on Hematological Oncology.
  • Place of Presentation: Nanjing, China.
  • Int'l Joint Research / Invited
• [Presentation] DYNAMICS OF CLONAL EVOLUTION IN MYELODYSPLASTIC SYNDROMES. (2016)
  • Author(s): Hideki Makishima et al.
  • Organizer: 21st Congress of European Hematology Association.
  • Place of Presentation: Copenhagen, Denmark.
• [Presentation] Clonal dynamics in myelodysplastic syndromes. (2016)
  • Author(s): Hideki Makishima.
  • Organizer: The Japanese Society of Medical Oncology Annual Meeting.
  • Place of Presentation: 神戸
• [Presentation] Mutational panel for following clonal evolution in myelodysplastic syndromes. (2016)
  • Author(s): Hideki Makishima et al.
  • Organizer: The 78th Annual Meeting of the Japanese Society of Hematology.
  • Place of Presentation: 横浜
• [Presentation] Clinical impact of somatic mutations on clonal evolution in myelodysplastic syndromes. (2016)
  • Author(s): Hideki Makishima et al.
  • Organizer: The 75th Annual Meeting of the Japanese Cancer Association.
  • Place of Presentation: 横浜
• [Presentation] Distinct genetic events in PNH and AA. (2016)
  • Author(s): Hideki Makishima.
  • Organizer: 2016 Annual Scientific Meeting, The International PNH Interest Group.
  • Place of Presentation: San Diego, USA.
  • Int'l Joint Research / Invited
• [Presentation] The Impact of Clonal Dynamics on Prognosis and Outcome in Myelodysplastic Syndromes. (2016)
  • Author(s): Hideki Makishima et al.
  • Organizer: 58th Annual Meeting of American Society of Hematology.
  • Place of Presentation: San Diego, USA.
• [Remarks] Researchmap
  • URL: https://researchmap.jp/read0132488/?lang=english
• [Remarks] ライフサイエンスレビュー
  • URL: http://first.lifesciencedb.jp/archives/15045
• [Remarks] 京都大学 プレスリリース
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2016/161220_1.html
• [Remarks] 東京大学 医科学研究所 発表論文解説
  • URL: http://www.ims.u-tokyo.ac.jp/imsut/jp/research/papers/_2.php