Studies of MDS pathogenesis and its relation to novel therapeutic strategies

• Project/Area Number: 20H00537
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: KITAMURA TOSHIO 東京大学, 大学院薬学系研究科(薬学部), 名誉教授 (20282527)
• Co-Investigator(Kenkyū-buntansha): 井上 大地 公益財団法人神戸医療産業都市推進機構, その他部局等, 研究員(副センター長・部長クラス) (80735746)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥44,980,000 (Direct Cost: ¥34,600,000、Indirect Cost: ¥10,380,000); Fiscal Year 2023: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000); Fiscal Year 2022: ¥11,440,000 (Direct Cost: ¥8,800,000、Indirect Cost: ¥2,640,000); Fiscal Year 2021: ¥12,350,000 (Direct Cost: ¥9,500,000、Indirect Cost: ¥2,850,000); Fiscal Year 2020: ¥13,260,000 (Direct Cost: ¥10,200,000、Indirect Cost: ¥3,060,000)
• Keywords: MDS / ASXL1 / クローン性造血 / PPI / 骨髄異形成症候群 / スプライシング

Outline of Research at the Start

骨髄異形成症候群(myelodysplastic syndromes: MDS)は多くの染色体異常や100種類以上の遺伝子変異が同定されている難治性の造血器腫瘍である。MDSは近年の人口高齢化に伴い増加し、病因も不明であり有効な 治療法が確立されていない。平均生存期間もハイリスク群では1年未満と他の悪性腫瘍に比較して悪く、AMLに移行すると通常のAMLと比べて治療が極めて難しい。DNAメチル化阻害剤による治療では約30%のMDS患者で輸血の必要性が減少するなど一定の効果が確認されたが、生存率延長は十分とは言えない。そのため、MDSの病因解明と治療法の開発に繋がる研究は重要である。

Outline of Final Research Achievements

By analyzing various mouse models, we have elucidated some of the causes of pancytopenia in myelodysplastic syndromes (MDS), a heterogeneous disease. In addition, a new MDS model was generated by crossing mutant ASXL1 knock-in mice with STAG2 knock-out mice to elucidate the pathogenic mechanism. Our results demonstrate that mutations in the epigenomic factor ASXL1 not only contribute to MDS pathogenesis via aberrant gene expression, but also induce DNA damage by activating the Akt-mTOR pathway in the cytosol.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会の日本では2025年に65歳以上の人口が30%を超える。中でも高齢者に多い骨髄異形成症候群（MDS）を発症する患者は増え続けている。MDS、AML、心筋梗塞、脳梗塞、糖尿病、固形癌、骨粗鬆症、慢性関節リウマチなど多くの疾患の温床となるクローン性造血（CH）も大きな社会問題である。CHとは65歳以上の10人に１人でASXL1変異など白血病関連遺伝子を一つ有する造血クローンが増生することである。本研究によって同定した変異型ASXL1によるシグナル伝達経路の活性化はASXL1変異を有するCHにおいて治療標的となりうる。CHから疾患の発症原因を明らかにすることは学術的にも重要である。

Research Products

• [Journal Article] CHIP‐associated mutant ASXL1 in blood cells promotes solid tumor progression (2022)
  • Author(s): Liu Xiaoxiao、Sato Naru、Shimosato Yuko、Wang Teh‐Wei、Denda Tamami、Chang Yu‐Hsuan、Yabushita Tomohiro、Fujino Takeshi、Asada Shuhei、Tanaka Yosuke、Fukuyama Tomofusa、Enomoto Yutaka、Ota Yasunori、Sakamoto Takeharu、Kitamura Toshio、Goyama Susumu
  • Journal Title: Cancer Science Volume: 113 Issue: 4 Pages: 1182-1194
  • DOI: 10.1111/cas.15294
  • Peer Reviewed / Open Access
• [Journal Article] MDS cells impair osteolineage differentiation of MSCs via extracellular vesicles to suppress normal hematopoiesis. (2022)
  • Author(s): Hayashi Y, Inoue D, et al.
  • Journal Title: Cell Reports Volume: VOLUME 39, ISSUE 6 Issue: 6 Pages: 110805-110805
  • DOI: 10.1016/j.celrep.2022.110805
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Multi-omics analysis defines highly refractory RAS burdened immature subgroup of infant acute lymphoblastic leukemia (2022)
  • Author(s): Tomoya Isobe, Masatoshi Takagi, Aiko Sato-Otsubo, et al. (57人中28番目)
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 4501-4501
  • DOI: 10.1038/s41467-022-32266-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mechanisms involved in hematopoietic stem cell aging (2022)
  • Author(s): Fujino Takeshi、Asada Shuhei、Goyama Susumu、Kitamura Toshio
  • Journal Title: Cellular and Molecular Life Sciences Volume: 79 Issue: 9 Pages: 473-473
  • DOI: 10.1007/s00018-022-04356-5
  • Peer Reviewed / Open Access
• [Journal Article] UBC9 inhibits myeloid differentiation in collaboration with AML1-MTG8 (2022)
  • Author(s): Fukuyama Tomofusa、Kitamura Toshio、Kozu Tomoko
  • Journal Title: International Journal of Hematology Volume: 115 Issue: 5 Pages: 686-693
  • DOI: 10.1007/s12185-022-03303-1
  • Peer Reviewed / Open Access
• [Journal Article] RUNX1 Inhibition Using Lipid Nanoparticle-Mediated Silencing RNA Delivery as an Effective Treatment for Acute Leukemias (2022)
  • Author(s): Iida Kohei、Tsuchiya Akiho、Tamura Moe、Yamamoto Keita、Kawata Shigehisa、Ishihara-Sugano Mitsuko、Kato Motohiro、Kitamura Toshio、Goyama Susumu
  • Journal Title: Experimental Hematology Volume: 112-113 Pages: 1-8
  • DOI: 10.1016/j.exphem.2022.05.001
  • Peer Reviewed / Open Access
• [Journal Article] IMPDH inhibition activates TLR‐VCAM1 pathway and suppresses the development of MLL‐fusion leukemia (2022)
  • Author(s): Liu Xiaoxiao、Sato Naru、Yabushita Tomohiro、Li Jingmei、Jia Yuhan、Tamura Moe、Asada Shuhei、 Fujino Takeshi、Fukushima Tsuyoshi、Yonezawa Taishi、Tanaka Yosuke、et al. O'Brien Eric、 Mizukawa Benjamin、Mulloy James C、Sugiura Yuki、Takizawa Hitoshi、Shibata Takuma、Miyake Kensuke、Kitamura Toshio、Goyama Susumu
  • Journal Title: EMBO Molecular Medicine Volume: 15 Issue: 1
  • DOI: 10.15252/emmm.202115631
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Eliminating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors (2022)
  • Author(s): Tanaka Yosuke....Goyama Susumu、Komatsu Norio、Takaku Tomoiku、Kitamura Toshio
  • Journal Title: Nature Communications Volume: 13 Issue: 1 Pages: 271-271
  • DOI: 10.1038/s41467-021-27928-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impaired osteoblastic differentiation of MSCs suppresses normal hematopoiesis in MDS. (2022)
  • Author(s): Hayashi, Y., Kawabata, K.C., Tanaka, Y., Uehara, Y., Kiryu, S., Ota, Y., Yoshioka, Y., Mabuchi, Y., Sugiyama, T., Mikami, K., Tamura, M., Fukushima, T., Asada, S., Takeda, R., Kunisaki, Y., Fukuyama, T., Goyama, S., Yokoyama, K., Tojo, A., Katayama, Y., Arai, F., Nagasawa, T., Ochiya, T., Inoue, D., and Kitamura, T.
  • Journal Title: Cell Rep Volume: -
  • Peer Reviewed
• [Journal Article] Eradicating chronic myeloid leukemia stem cells by IRAK1/4 inhibitors (2021)
  • Author(s): Tanaka, Y., Fukushima, T., Mikami, K., Tsuchiya, S., Tamura, M., Adachi, K., Umemoto, T., Watanabe, N., Morishita, S., Imai, M., Nagata, M., Araki, M., Takizawa, H., Fukuyama, T., Lamagna, C., Masuda, E., Ito, R., Goyama, S., Komatsu, N., Takaku, T., and Kitamura, T.
  • Journal Title: Nature Communications Volume: 13
  • DOI: 10.21203/rs.3.rs-449398/v1
  • Peer Reviewed
• [Journal Article] CRISPR/Cas9-mediated base-editing enables a chain reaction through sequential repair of sgRNA scaffold mutations (2021)
  • Author(s): Fukushima, T., Tanaka, Y., Adachi, K., Masuyama, N., Tsuchiya, A., Asada, S., Ishiguro, S., Mori, H., Seki, M., Yachie, N., Goyama, S., Kitamura, T.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1
  • DOI: 10.1038/s41598-021-02986-6
  • Peer Reviewed / Open Access
• [Journal Article] A histone modifier, ASXL1, interacts with NONO and is involved in paraspeckle formation in hematopoietic cells (2021)
  • Author(s): Yamamoto Keita、Goyama Susumu、Asada Shuhei、Fujino Takeshi、Yonezawa Taishi、Sato Naru、Takeda Reina、Tsuchiya Akiho、Fukuyama Tomofusa、Tanaka Yosuke、Yokoyama Akihiko、Toya Hikaru、Kon Ayana、Nannya Yasuhito、Onoguchi-Mizutani Rena、Nakagawa Shinichi、Hirose Tetsuro、Ogawa Seishi、Akimitsu Nobuyoshi、Kitamura Toshio
  • Journal Title: Cell Reports Volume: 36 Issue: 8 Pages: 109576-109576
  • DOI: 10.1016/j.celrep.2021.109576
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive expression pattern of kin of irregular chiasm-like 3 in the adult mouse brain (2021)
  • Author(s): Hisaoka, T., Komori, T., Fujimoto, K., Kitamura, T., and Morikawa, Y.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 563 Pages: 66-72
  • DOI: 10.1016/j.bbrc.2021.05.063
  • Peer Reviewed
• [Journal Article] Clonal hematopoiesis and associated diseases: A review of recent findings (2021)
  • Author(s): Shuhei Asada, Toshio Kitamura
  • Journal Title: Cancer Science Volume: 112 Issue: 10 Pages: 3962-3971
  • DOI: 10.1111/cas.15094
  • Peer Reviewed / Open Access
• [Journal Article] Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cell through activation of Akt/mTOR pathway. (2021)
  • Author(s): Fujino, T., Goyama, S., Sugiura, Y., Inoue, D., Asada, S., Yamasaki, S., Matsumoto, A., Tsuchiya, A., Shikata, S., Sato N., Morinaga, H., Fukuyama, T., Tanaka, Y., Fukushima, T., Takeda, R., Yamamoto, K., Honda, H., Nishimura, E.K., Shibata, T., Abdel-Wahab, Omar., Suematsu, M., and Kitamura, T.
  • Journal Title: nature communications Volume: 12 Pages: 1826-1826
  • Peer Reviewed / Open Access
• [Journal Article] Imaging dynamic mTORC1 pathway activity in vivo reveals marked shifts that support time-specific inhibitor therapy in AML. (2021)
  • Author(s): Oki, T., Mercier, F., Kato, H., Jung, Y., McDonald, T., Spencer, J., Mazzola, M., Gastel, N.V., Lin, C., Michor, F., Kitamura, T., and Scadden, D.
  • Journal Title: nature communications Volume: 12 Pages: 245-245
  • Peer Reviewed / Open Access
• [Journal Article] Minor intron retention drives clonal hematopoietic disorders and diverse cancer predisposition (2021)
  • Author(s): Inoue D, Polaski JT, Taylor J, Castel P, Chen S, Kobayashi S, Hogg SJ, Hayashi Y, Fukumoto M, Yamazaki H, Tanaka A, Fukui C, Chew GL, McCormick F, Bradley RK, Abdel-Wahab O.
  • Journal Title: Nature Genetics Volume: 21 Issue: 5 Pages: 828-828
  • DOI: 10.1038/s41588-021-00828-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Efficacy of tyrosine kinase inhibitors on a mouse chronic myeloid leukemia model and chronic myeloid leukemia stem cells. (2020)
  • Author(s): Tanaka, Y., Fukushima, T., Mikami, K., Adachi, K., Fukuyama, T., Goyama, S., and Kitamura, T.
  • Journal Title: Exp Hematol Volume: 90 Pages: 46-51
  • Peer Reviewed / Open Access
• [Journal Article] Activation of CpG-Rich Promoters Mediated by MLL Drives MOZ-Rearranged Leukemia (2020)
  • Author(s): Miyamoto Ryo、Okuda Hiroshi、Kanai Akinori、Takahashi Satoshi、Kawamura Takeshi、Matsui Hirotaka、Kitamura Toshio、Kitabayashi Issay、Inaba Toshiya、Yokoyama Akihiko
  • Journal Title: Cell Reports Volume: 32 Issue: 13 Pages: 108200-108200
  • DOI: 10.1016/j.celrep.2020.108200
  • Peer Reviewed / Open Access
• [Journal Article] HHEX promotes myeloid transformation in cooperation with mutant ASXL1. (2020)
  • Author(s): Takeda R, Asada S, Park SJ, Yokoyama A, Becker H, Kanai A, Visconte V, Hershberger C, Hayashi Y, Yonezawa T, Tamura M, Fukushima T, Tanaka Y, Fukuyama T, Matsumoto A, Yamasaki S, Nakai K, Yamazaki S, Inaba T, Shibata T, Inoue D, Honda H, Goyama S, Maciejewski J, Kitamura T.
  • Journal Title: Blood Volume: 136 Pages: 1670-1684
  • DOI: 10.1182/blood.2019004613
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Understanding and therapeutic targeting of aberrant mRNA splicing mechanisms in oncogenesis (2020)
  • Author(s): 田中 淳、小林 漸、肖 慕然、井上 大地
  • Journal Title: Rinsho Ketsueki Volume: 61 Issue: 6 Pages: 643-650
  • DOI: 10.11406/rinketsu.61.643
  • NAID: 130007869132
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed / Open Access
• [Presentation] 骨髄異形成症候群(MDS)細胞は miRNA を骨髄ニッチに送り込むことによって正常造血を抑制する:MDS における正常造血抑制機序の一例 (2023)
  • Author(s): 北村 俊雄
  • Organizer: 第7回日本骨免疫学会冬季学術集会
  • Invited
• [Presentation] Clonal hematopoiesis, inflammation and cardiovascular diseases (2023)
  • Author(s): Toshio Kitamura
  • Organizer: 2023 Normal/Malignant Hematopoiesis and Novel Therapies for Hematologic Malignancies Symposium
  • Int'l Joint Research
• [Presentation] CRISPR-dCas9 activation全ゲノムスクリーニング法による骨髄系腫瘍に対するDecitabineの作用機序の解明 (2023)
  • Author(s): 藪下 知宏、知念 拓実、西山 敦哉、南谷 泰仁、中西 真、北川 大樹、北村 俊雄、合山 進
  • Organizer: 第40 回染色体ワークショップ、第21回核ダイナミクス研究会
• [Presentation] A novel G0 marker identifies leukemic stem cells of CML which could be targeted by PD1/PDL1 antibodies or an IRAK (2022)
  • Author(s): Toshio Kitamura
  • Organizer: 24th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy
  • Int'l Joint Research / Invited
• [Presentation] クローン性造血と造血器腫瘍 (2022)
  • Author(s): 北村 俊雄
  • Organizer: 第22回日本抗加齢医学会総会
  • Invited
• [Presentation] クローン性造血と動脈硬化の関係性 (2022)
  • Author(s): 北村 俊雄
  • Organizer: 第70回日本心臓病学会学術集会
  • Invited
• [Presentation] ASXL1によるパラスペックル制御と白血病 (2022)
  • Author(s): 山本圭太、合山進、北村俊雄
  • Organizer: 第81回日本癌学会学術総会
• [Presentation] In vivo CRISPR/Cas9ライブラリスクリーニングにより明らかとなった 急性骨髄性白血病におけるAtp2a2の腫瘍抑制因子としての役割 (2022)
  • Author(s): 志村瑠香、北村俊雄、合山進
  • Organizer: 第81回日本癌学会学術総会
• [Presentation] Decitabine induces excessive DNA-DNMT1 crosslinks and perturbs faithful mitosis of myeloid tumors (2022)
  • Author(s): Tomohiro Yabushita, Shuhei Asada, Keita Yamamoto, Naru Sato, Yutaka Enomoto, Yosuke Tanaka, Tomofusa Fukuyama, Atsuya Nishiyama, Makoto Nakanishi, Toshio Kitamura, Susumu Goyama
  • Organizer: The 84rd Annual Meeting of JSH
  • Int'l Joint Research
• [Presentation] MECOM症候群で認められる変異は、MECOMの転写活性化能及び造腫瘍性を喪失させる (2022)
  • Author(s): 飯田孝平、山本圭太、浅田修平、北村俊雄、合山進
  • Organizer: 第84回日本血液学会
• [Presentation] Mitotic Perturbation Is a Key Mechanism of Action of Decitabine in Myeloid Tumor Treatment (2022)
  • Author(s): Tomohiro Yabushita, Takumi Chinen, Atsuya Nishiyama, Shuhei Asada, Keita Yamamoto, Naru Sato, Yutaka Enomoto, osuke Tanaka, Keiko Katoh, Kaori Saitoh, Takamasa Ishikawa, Hitoshi Sato, Tomoyoshi Soga, Yasuhito Nannya, Makoto Nakanishi, Daiju Kitagawa, Toshio Kitamura, Susumu Goyama
  • Organizer: 64th American Society of Hematology (ASH) Annual Meeting and Exposition New Orleans
  • Int'l Joint Research
• [Presentation] MECOM 症候群で認められる変異は、MECOM の転写活性化能及び造腫瘍性を喪失させる (2022)
  • Author(s): 飯田孝平、山本圭太 、浅田修平 、北村俊雄 、合山進
  • Organizer: 第27回造血器腫瘍研究会
• [Presentation] Identification of tumor regulators in myeloid neoplasms using in vivo CRISPR-Cas9 screening (2022)
  • Author(s): Yu-Hsuan Chang, Takeshi Fujino,Toshio Kitamura, Susumu Goyama2
  • Organizer: 第27回造血器腫瘍研究会
• [Presentation] Chronal hematopoiesis and related disorders (2022)
  • Author(s): 北村俊雄
  • Organizer: JSPS Core-to-Core Program(A.Advanced Research Networks)Symposium
  • Int'l Joint Research / Invited
• [Presentation] Chronal hematopoiesis and related disorders caused by epigenetic factors (2022)
  • Author(s): 北村俊雄
  • Organizer: 鶴岡カンファレンス２０２１
  • Int'l Joint Research / Invited
• [Presentation] Biochemical and functional analysis of STUB1-HSP70/90 complex (2022)
  • Author(s): 郭楊穎、合山進
  • Organizer: 新学術領域研究「ケモユビキチン」第4回若手主体発表会
• [Presentation] クローン性造血 (2021)
  • Author(s): 北村俊雄
  • Organizer: 第83回日本血液学会学術集会
  • Invited
• [Presentation] CHIP-ASSOCIATED MUTANT ASXL1 ACTIVATES INNATE IMMUNE PATHWAY IN MYELOID CELLS AND PROMOTES ATHEROSCLEROSIS IN MICE (2021)
  • Author(s): 佐藤成、合山進、張育宣、藤野赳至、浅田修平、四方紫織、劉瀟瀟、米澤大志、竹田玲奈、山本圭太、柴田琢磨、関谷元博、小出周平、岩間厚志、三宅健介、島野仁、北村俊雄
  • Organizer: 26th Congress of the European Hematology Association
  • Int'l Joint Research
• [Presentation] Biochemical and functional analysis of STUB1-HSP70/90 complex (2021)
  • Author(s): 郭楊穎、合山進
  • Organizer: 新学術領域研究「ケモユビキチン」第3回若手主体発表会
• [Presentation] Sema6b is required for adequate distribution of mature myeloid cells in vivo (2021)
  • Author(s): 福山朋房、川崎能彦、宮井智浩、山本圭太、長町安希子、稲葉俊哉、伊川友活、平田たつみ、北村俊雄
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] イマチニブとIRAK1/4 阻害剤との併用は慢性骨髄性白血病幹細胞の駆逐に効果的である (2021)
  • Author(s): 田中洋介、竹田玲奈、福島剛、合山進、北村俊雄
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] リピッドナノパーティクルを活用したRUNX1ノックダウンは、T細胞白血病の増殖を抑制する (2021)
  • Author(s): 飯田孝平、土屋秋穂、川田滋久、菅野美津子、合山進
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] A histone modifier ASXL1 interacts with NONO and is involved in paraspeckle formation in hematopoietic cells (2021)
  • Author(s): 山本圭太、合山進、浅田修平、藤野赳至、米澤太志、佐藤成、竹田玲奈、福山朋房、田中洋介、横山明彦、昆彩奈、南谷泰仁、小野口玲菜、秋光信佳、小川誠司、北村俊雄
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] Hyperactive NK cells in Rag2-deficient mice suppress the development of acute myeloid leukemia (2021)
  • Author(s): 杉本絵美、合山進、林康貴、浅田修平、福島剛、川瀬竜也、斎藤健、吉田卓、山崎聡、海渡裕太、今井陽一、福山朋房、田中洋介、榎本豊、北村俊雄
  • Organizer: 第83回日本血液学会学術集会
• [Presentation] p53活性化薬は、NK細胞と協調して急性骨髄性白血病の発症を抑制する (2021)
  • Author(s): 合山進、杉本絵美、北村俊雄
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] Hyperactive NK cells in Rag2-deficient mice suppress the development of acute myeloid leukemia (2021)
  • Author(s): 杉本絵美、合山進、林康貴、浅田修平、海渡裕太、今井陽一、福山朋房、田中洋介、北村俊雄
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] Somatic ASXL1 mutation in blood cells promote solid tumor progression (2021)
  • Author(s): 劉瀟瀟、佐藤成、北村俊雄、合山進
  • Organizer: 第80回日本癌学会学術総会
• [Presentation] Combination of ASXL1 mutation and Stag2 loss leads to development of myelodysplastic syndromes (2021)
  • Author(s): 藤野赳至、越智陽太郎、昆彩奈、合山進、小川誠司、北村俊雄
  • Organizer: ISEH 2021 Virtual Scientific Meeting
  • Int'l Joint Research
• [Presentation] PROGRESSIVE IN VIVO KINETIC PAIRED DAUGHTER CELL (PINK-PDC) ASSAY REVEALS NOVEL HSC FEATURES (2021)
  • Author(s): 田中洋介、福島剛、山本圭太、合山進、北村俊雄
  • Organizer: ISEH 2021 Virtual Scientific Meeting
  • Int'l Joint Research
• [Presentation] ASXL1変異を伴う血液細胞が固形腫瘍の発症、進展に及ぼす影響 (2021)
  • Author(s): 劉瀟瀟
  • Organizer: 第25回造血器腫瘍研究会
• [Presentation] Asxl1 と Stag2 の変異は協調して遺伝子発現を変化させ骨髄異形成症候群の発症を誘導する (2021)
  • Author(s): 藤野赳至、越智陽太郎、昆彩奈、合山進、小川誠司、北村俊雄
  • Organizer: 第25回造血器腫瘍研究会
• [Presentation] 造血幹・前駆細胞におけるASXL1変異による核内構造体形成異常の解析 (2021)
  • Author(s): 山本圭太、合山進、浅田修平、藤野赳至、米澤太志、佐藤成、竹田玲奈、福山朋房、田中洋介、横山明彦、昆彩奈、南谷泰仁、小川誠司、北村俊雄
  • Organizer: 第25回造血器腫瘍研究会
• [Presentation] クローン性造血におけるミトコンドリア活性化とDNAダメージ亢進 (2020)
  • Author(s): 北村俊雄
  • Organizer: 鶴岡カンファレンス２０２０
  • Invited
• [Presentation] Clonal Hematopoiesis Associated with Mutant ASXL1 Accelerates Atherosclerosis in Mice (2020)
  • Author(s): 佐藤成、合山進、浅田修平、藤野赳至、劉瀟瀟、竹田玲奈、山本圭太、米澤大志、北村俊雄
  • Organizer: 第82回日本血液学会学術集
• [Presentation] IRAK1/4-NFkB-PDL1 axis is important for maintenance of CML-LSCs (2020)
  • Author(s): 田中洋介、合山進、北村俊雄
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] DTX2はRUNX1のユビキチン化および脱アセチル化を促進し、白血病細胞の増殖を抑制する (2020)
  • Author(s): 米澤大志、北村俊雄、合山進
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] DTX2はRUNX1のユビキチン化および脱アセチル化を促進し、白血病細胞の増殖を抑制する (2020)
  • Author(s): 米澤大志、北村俊雄、合山進
  • Organizer: 第82回日本血液学会学術集会
• [Presentation] Combination of ASXL1 mutation and Stag2 loss lead to development of myelodysplastic syndromes (2020)
  • Author(s): 藤野赳至、越智陽太郎、昆彩奈、合山進、小川誠司、北村俊雄
  • Organizer: 第８２回日本血液学会学術集会
• [Presentation] Mutant ASXL1 induces expansion of hematopoietic stem cells through activation of Akt/mTOR pathway (2020)
  • Author(s): 藤野赳至、合山進、Yuki Sugiura、井上大地、浅田修平、Satoshi Yamasaki、Akiko Matsumoto、Kiyoshi Yamaguchi、土屋秋穂、四方紫織、佐藤成、Hironobu Morinaga、福山朋房、田中洋介、福島剛、竹田玲奈、山本圭太、本田浩章、Emi K. Nishimura、古川洋一、Tatsuhiro Shibata、Omar Abdel-Wahab、末松誠、北村俊雄
  • Organizer: ISEH 2020 Virtual Scientific Meeting
  • Int'l Joint Research
• [Presentation] Epigenetic Regulator ASXL1 Promotes Paraspeckle Formation through C-terminal Intrinsically Disordered Region in Hematopoietic Cells (2020)
  • Author(s): 山本圭太、合山進、北村俊雄
  • Organizer: ISEH 2020 Virtual Scientific Meeting
  • Int'l Joint Research
• [Presentation] Epigenetic Regulator ASXL1 Promotes Paraspeckle Formation through C-terminal Intrinsically Disordered Region in Hematopoietic Cells (2020)
  • Author(s): 山本圭太、合山進、浅田修平、藤野赳至、米澤太志、佐藤成、竹田玲奈、福山朋房、田中洋介、北村俊雄
  • Organizer: Call for presentations for IMSUT Presentation of Research Findings 2020
  • Int'l Joint Research
• [Presentation] スプライシング異常を介した新規発がん機構 (2020)
  • Author(s): 井上大地
  • Organizer: 第92回日本遺伝学会ワークショップ
• [Presentation] Clarifying the Role of Minor Introns in Cancer Predisposition (2020)
  • Author(s): 井上大地
  • Organizer: 4th CCII Seminar
• [Presentation] マイナーイントロンを介した発癌機構 (2020)
  • Author(s): 井上大地
  • Organizer: 鶴岡カンファレンス2020
• [Presentation] イントロンから発癌を読み解く (2020)
  • Author(s): 井上大地
  • Organizer: 東京血液懇話会
• [Presentation] 造血幹細胞を中心とした多細胞間の適応・修復ネットワークの解明と制御 (2020)
  • Author(s): 井上大地
  • Organizer: AMED-CREST/PRIMEキックオフ・領域会議
• [Presentation] RNAの視点からみた造血器腫瘍 (2020)
  • Author(s): 井上大地
  • Organizer: 第11回神奈川MDS研究会
• [Presentation] スプライシング異常から紐解く造血器腫瘍 (2020)
  • Author(s): 井上大地
  • Organizer: 第３回先端医科学研究センター「マルチオミックスによる遺伝子現制御の先端的医学共同研究拠点」セミナー
• [Presentation] ZRSR2 Mutation Induced Minor Intron Retention Drives MDS and Diverse Cancer Predisposition Via Aberrant Splicing of LZTR1 (2020)
  • Author(s): 井上大地
  • Organizer: The 62nd ASH Annual Meeting and Exposition
• [Presentation] Impaired Osteoblastic Differentiation of MSCs Suppresses Normal Hematopoiesis in MDS (2020)
  • Author(s): 林康貴
  • Organizer: The 62nd ASH Annual Meeting and Exposition