Glycosilation of glycosaminoglycan in bone marrow affect in hematopoiesis and GVHD after BM transplantation

• Project/Area Number: 16K09868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Niigata University
• Principal Investigator: MASUKO MASAYOSHI 新潟大学, 医歯学総合病院, 准教授 (70397115)
• Co-Investigator(Kenkyū-buntansha): 五十嵐 道弘 新潟大学, 医歯学系, 教授 (50193173) ; 牛木 隆志 新潟大学, 医歯学総合病院, 講師 (80579152)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: コンドロイチン硫酸 / 造血幹細胞 / 造血ニッチ / 造血分化 / 骨髄間質 / 骨髄造血 / 末梢神経障害 / 骨髄グリコサミノグリカン / 造血細胞移植 / ＧＶＨＤ

Outline of Final Research Achievements

Chondroitin sulfate (CS), a glycosaminoglycan, is a major component of the extracellular matrix; however, it is not known whether CS has a physiological role in the hematopoiesis in BM. We analyzed the effects of CS on the BM microenvironment using knockout of N-acetylgalactosaminyltransferase-1, a key enzyme for CS biosynthesis that is important for regulating CS levels. HSPCs from T1KO mice showed significantly impaired repopulation in WT recipient mice upon serial transplantation. In contrast, the number of WT HSPCs repopulated in T1KO recipient mice was greater than that in WT recipient mice after serial transplantation, indicating that the T1KO BM niche supports repopulation of HSPCs better than the WT BM niche. RNA sequence analysis revealed that HSPCs in T1KO is associated with activation of the IFN-α/β signal and endoplasmic reticulum stress.

Academic Significance and Societal Importance of the Research Achievements

本研究によりコンドロイチン硫酸は造血ニッチ、造血幹細胞それぞれで造血分化に異なる作用を示すことが明らかになった。造血細胞移植時の前処置、老化によりコンドロイチン硫酸量は変化しすると考えられ、本研究の結果は糖鎖修飾による造血細胞移植後の生着促進や老化に伴う造血不全症、白血病の新しい視点からの治療法の開発につながる。

Research Products

• [Journal Article] The Glasgow prognostic score divides high-risk hematopoietic cell transplantation-specific comorbidity index patients into stratified subgroups in allogeneic hematopoietic cell transplantation (2020)
  • Author(s): Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Fuse Kyoko、Narita Miwako、Sone Hirohito、Masuko Masayoshi
  • Journal Title: Annals of Hematology Volume: 99 Issue: 3 Pages: 671-673
  • DOI: 10.1007/s00277-020-03936-4
  • Peer Reviewed
• [Journal Article] Time-Varying Effects of Graft Type on Outcomes for Patients with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation (2020)
  • Author(s): Yanada M, Konuma T, Yamasaki S, Kuwatsuka Y, Masuko M, Tanaka M, Ozawa Y, Toya T, Fukuda T, Ota S, Sawa M, Uchida N, Nakamae H, Eto T, Kanda J, Takanashi M, Kanda Y, Atsuta Y, Yano S.
  • Journal Title: Biology of Blood and Marrow Transplantation Volume: 26 Issue: 2 Pages: 307-315
  • DOI: 10.1016/j.bbmt.2019.09.036
  • Peer Reviewed
• [Journal Article] Using a machine learning algorithm to predict acute graft-versus-host disease following allogeneic transplantation. (2019)
  • Author(s): Arai Y, Kondo T, Fuse K, Shibasaki Y, Masuko M, Sugita J, Teshima T, Uchida N, Fukuda T, Kakihana K, Ozawa Y, Eto T, Tanaka M, Ikegame K, Mori T, Iwato K, Ichinohe T, Kanda Y, Atsuta Y.
  • Journal Title: Blood Adv. Volume: 3(22) Issue: 22 Pages: 3626-3634
  • DOI: 10.1182/bloodadvances.2019000934
  • NAID: 120006817456
  • Peer Reviewed / Open Access
• [Journal Article] Clinical practice recommendations for the diagnosis and management of human herpesvirus-6B encephalitis after allogeneic hematopoietic stem cell transplantation: the Japan Society for Hematopoietic Cell Transplantation. (2019)
  • Author(s): Ogata M, Uchida N, Fukuda T, Ikegame K, Kamimura T, Onizuka M, Kato K, Kobayashi H, Sasahara Y, Sawa M, Sawada A, Hasegawa D, Masuko M, Miyamoto T, Okamoto S.
  • Journal Title: Bone Marrow Transplant. Volume: -- Issue: 6 Pages: 1004-1013
  • DOI: 10.1038/s41409-019-0752-5
  • Peer Reviewed
• [Journal Article] Patient-based Prediction Algorithm of Relapse After allo-HSCT for Acute Leukemia and Its Usefulness in the Decision-Making Process Using a Machine Learning Approach (2019)
  • Author(s): Fuse K, Uemura S, Tamura S, Suwabe T, Katagiri T, Tanaka T, Ushiki T, Shibasaki Y, Sato N, Yano T, Kuroha T, Hashimoto S, Furukawa T, Narita M, Sone H, Masuko M.
  • Journal Title: Cancer Med. Volume: Sep;8(11) Issue: 11 Pages: 5058-5067
  • DOI: 10.1002/cam4.2401
  • Peer Reviewed / Open Access
• [Journal Article] Rh null Phenotype Caused by a Novel RHAG Mutation, c.945+1G>A, in the Japanese Population (2019)
  • Author(s): Ushiki T, Tsuneyama H, Masuko M, Kozakai T, Kasami T, Tanaka T, Uchikawa M, Kitajima T, Kasai E, Komata T, Katagiri T, Kamimura M, Sato K, Fuse I, Ogasawara K, Nakata K.
  • Journal Title: Transfusion Volume: Aug;59(8) Issue: 8 Pages: 2519-2522
  • DOI: 10.1111/trf.15312
  • Peer Reviewed
• [Journal Article] Patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: trends in survival during the past two decades (2018)
  • Author(s): Yanada Masamitsu,Masuko Masayosh,Mori Jinich,Aoki Ju,Mizuno Shohe,Fukuda Takahiro、Kakihana Kazuhiko、Ozawa Yukiyasu、Ota Shuichi、Kanamori Heiwa、Mori Takehiko、Nakamae Hirohisa、Eto Tetsuya、Shiratori Souichi、Maeda Tetsuo、Iwato Koji、Ichinohe Tatsuo、Kanda Yoshinobu、Tanaka Junji、Atsuta Yoshiko、Yano Shingo
  • Journal Title: Bone Marrow Transplantation Volume: 54 Issue: 4 Pages: 578-586
  • DOI: 10.1038/s41409-018-0301-7
  • Peer Reviewed
• [Journal Article] Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation (2018)
  • Author(s): Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Tanaka Tomoyuki、Ushiki Takashi、Fuse Kyoko、Sato Naoko、Yano Toshio、Kuroha Takashi、Hashimoto Shigeo、Narita Miwako、Furukawa Tatsuo、Sone Hirohito、Masuko Masayoshi
  • Journal Title: International Journal of Hematology Volume: 108 Issue: 3 Pages: 282-289
  • DOI: 10.1007/s12185-018-2463-x
  • Peer Reviewed
• [Journal Article] Effects of eculizumab treatment on quality of life in patients with paroxysmal nocturnal hemoglobinuria in Japan (2018)
  • Author(s): Y. Ueda, N. Obara, Y. Yonemura, H. Noji, M. Masuko, Y. Seki, K. Wada, T. Matsuda, H. Akiyama, T. Ikezoe, S. Chiba, Y. Kanda, T. Kawaguchi, T. Shichishima, H. Nakakuma, S. Okamoto, J. Nishimura, Y. Kanakura, H. Ninomiya
  • Journal Title: International Journal of Hematology Volume: epub Issue: 6 Pages: 1-10
  • DOI: 10.1007/s12185-018-2409-3
  • Peer Reviewed
• [Journal Article] Outcomes after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia harboring t(7;11)(p15;p15). (2018)
  • Author(s): Harada K, Doki N, Aoki J, Mori J, Machida S, Masuko M, Uchida N, Najima Y, Fukuda T, Kanamori H, Ogawa H, Ota S, Ogawa K, Takahashi S, Kasai M, Maeda A, Nagafuji K, Kawakita T, Ichinohe T, Atsuta Y.
  • Journal Title: Hematologica Volume: 103(2) Issue: 2 Pages: e69-e72
  • DOI: 10.3324/haematol.2017.179804
  • Peer Reviewed / Open Access
• [Journal Article] MAGI-1 expression is decreased in several types of human T-cell leukemia cell lines, including adult T-cell leukemia. (2018)
  • Author(s): Kozakai T, Takahashi M, Higuchi M, Hara T, Saito K, Tanaka Y, Masuko M, Takizawa J, Sone H, Fujii M
  • Journal Title: International Journal of Hematology Volume: 107(3) Issue: 3 Pages: 337-344
  • DOI: 10.1007/s12185-017-2359-1
  • Peer Reviewed / Open Access
• [Journal Article] Functional dissection of hematopoietic stem cell populations with a stemness-monitoring system based on NS-GFP transgene expression (2017)
  • Author(s): Ali Mohamed A. E.、Fuse Kyoko、Tadokoro Yuko、Hoshii Takayuki、Ueno Masaya、Kobayashi Masahiko、Nomura Naho、Vu Ha Thi、Peng Hui、Hegazy Ahmed M.、Masuko Masayoshi、Sone Hirohito、Arai Fumio、Tajima Atsushi、Hirao Atsushi
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 11442-11442
  • DOI: 10.1038/s41598-017-11909-3
  • Peer Reviewed / Open Access
• [Journal Article] The Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation (2017)
  • Author(s): Shibasaki Yasuhiko、Suwabe Tatsuya、Katagiri Takayuki、Tanaka Tomoyuki、Kobayashi Hironori、Fuse Kyoko、Ushiki Takashi、Sato Naoko、Yano Toshio、Kuroha Takashi、Hashimoto Shigeo、Narita Miwako、Furukawa Tatsuo、Sone Hirohito、Masuko Masayoshi
  • Journal Title: Clinical Transplantation Volume: 31 Issue: 11
  • DOI: 10.1111/ctr.13103
  • Peer Reviewed / Open Access
• [Journal Article] Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies (2017)
  • Author(s): Tanaka Tomoyuki、Nakajima-Takagi Yaeko、Aoyama Kazumasa、Tara Shiro、Oshima Motohiko、Saraya Atsunori、Koide Shuhei、Si Sha、Manabe Ichiro、Sanada Masashi、Nakayama Manabu、Masuko Masayoshi、Sone Hirohito、Koseki Haruhiko、Iwama Atsushi
  • Journal Title: The Journal of Experimental Medicine Volume: 214 Issue: 10 Pages: 2901-2913
  • DOI: 10.1084/jem.20170167
  • Peer Reviewed / Open Access
• [Journal Article] Phase II study of intrabone single unit cord blood transplantation for hematological malignancies (2017)
  • Author(s): Murata Makoto、Maeda Yoshinobu、Masuko Masayoshi、et.al
  • Journal Title: Cancer Science Volume: 108 Issue: 8 Pages: 1634-1639
  • DOI: 10.1111/cas.13291
  • Peer Reviewed / Open Access
• [Journal Article] Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation. (2017)
  • Author(s): Hosokai R, Masuko M, Shibasaki Y, Saitoh A, Furukawa T, Imai C.
  • Journal Title: Biol Blood Marrow Transplant. Volume: 23(4) Issue: 4 Pages: 606-611
  • DOI: 10.1016/j.bbmt.2016.12.638
  • Peer Reviewed / Open Access
• [Journal Article] Successful umbilical cord blood hematopoietic stem cell transplantation in a patient with adult T-cell leukemia/lymphoma initially achieving complete remission with anti-CC chemokine receptor 4 antibody combined chemotherapy (2017)
  • Author(s): Suwabe T, Shibasaki Y, Kaihatsu A, Katagiri T, Miyakoshi S, Fuse K, Kobayashi H, Ushiki T, Moriyama M, Takizawa J, Narita M, Sone H, Masuko M.
  • Journal Title: Rinsho Ketsueki Volume: 58 Issue: 1 Pages: 32-36
  • DOI: 10.11406/rinketsu.58.32
  • NAID: 130005394599
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] The Dinakara equation for adjusting DLCO for hemoglobin in the HCT-CI is superior to the Cotes equation for predicting high-risk patients in allogeneic hematopoietic stem cell transplantation. (2016)
  • Author(s): Shibasaki Y, Katagiri T, Kobayashi H, Ushiki T, Narita M, Sone H, Furukawa T, Masuko M
  • Journal Title: Am J Hematol. Volume: Volume 91, Issue 5 Issue: 5
  • DOI: 10.1002/ajh.24318
  • Peer Reviewed
• [Presentation] Depletion of Pre-Transplant Skeletal Muscle Is Significant Poor Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation. (2019)
  • Author(s): Shibasaki Y, Kobayashi K, Suwabe T, Fuse K, Narita M, Sone H, Masuko M.
  • Organizer: 61st American Society of Hematology (ASH) Annual Meeting and Exposition.
  • Int'l Joint Research
• [Presentation] INTENSIVE ORAL CARE CAN REDUCE BLOOD STREAM INFECTION POST NEUTROPHIL ENGRAFTMENT IN ALLOGENEIC HSCT. (2019)
  • Author(s): Suwabe T, Fuse K, Katsura K, Tanaka K, Tamura S, Katairi T, Tanaka T, Ushiki T, Shibasaki Y, Narita M, Sone H, Masuko M.
  • Organizer: The 24th EHA (European Hematology Association) Congress.
  • Int'l Joint Research
• [Presentation] MARKER CHROMOSOME IS A STRONG POOR PROGNOSIS FACTOR AFTER ALLOGENEIC HSCT FOR AML PATIENTS. (2019)
  • Author(s): Fuse K, Tanaka T, Uemura S, Tamura S, Suwabe T, Katagiri T, Ushiki T, Shibasaki Y, Satou N, Yano T, Kuroha T, Hashimoto S, Furukawa T, Narita M, Sone H, Masuko M.
  • Organizer: The 24th EHA (European Hematology Association) Congress.
  • Int'l Joint Research
• [Presentation] SOCS3 Deficiency on a High-Fat Diet Accelerates Systemic Inflammation and Results in Lethal Myeloid Hematopoiesis without Obesity and Adiposity. (2019)
  • Author(s): Cho K, Ushiki T, Ishiguro H, Katagiri T, Suwabe T, Hirai H, Nakagawa Y, Masuko M, Alexander W, Shimano H, Sone H.
  • Organizer: 79th American Diabetes Association Scientific Sessions (ADA).
  • Int'l Joint Research
• [Presentation] Monitoring of Persistent CTLs over 10 Years Using MLPC after WT1 Peptide Vaccine in a CML Patient. (2019)
  • Author(s): Suwabe T, Ogawa S, Goto W, Sato H, Fuse K, Shibasaki Y, Sone H, Masuko M, Narita M.
  • Organizer: The 10th JSH International Symposium.
  • Int'l Joint Research
• [Presentation] Distinct Effects of Chondroitin Sulfate on Hematopoietic Cells and the Stromal Microenvironment in Bone Marrow Hematopoiesis (2018)
  • Author(s): Katagiri, T ; Ushiki, T ; Kawasaki, A ; Uemura, S ; Suwabe, T ; Tanaka, T ; Fuse, K ; Shibasaki, Y ; Sone, H ; Igarashi, M ; Masuko, M
  • Organizer: ASH annual meeting 2018
  • Int'l Joint Research
• [Presentation] Genetically Reduced Chondroitin Sulfate Prevents the Progression of Diabetic Neuropathy (2018)
  • Author(s): Ishiguro, H ; Ushiki, T ; Kawasaki, A ; Cho, K ; Masuko, M ; Sango, K; Igarashi, M ; Sone, H
  • Organizer: ADA annual meeting 2018
  • Int'l Joint Research
• [Presentation] Chondroitin sulfate contributes to the differentiation and the maintenance of hematopoietic cells (2018)
  • Author(s): Takayuki Katagiri, Takashi Ushiki, Asami Kawasaki, Shun Uemura, Tatsuya Suwabe, Tomoyuki Tanaka, Kyoko Fuse, Yasuhiko Shibasaki, Hirohito Sone, Michihiro Igarashi, Masayoshi Masuko
  • Organizer: JSH international synposium
  • Int'l Joint Research
• [Presentation] Genetically-reduced Chondroitin Sulfate Prevents the Progression of Diabetic Neuropathy. (2018)
  • Author(s): Hajime Ishiguro, Takashi Ushiki, Asami Kawasaki, Kaori Chou, Masayoshi Masuko, Kazunori Sango, Michihiro Igarashi, Hirohito Sone
  • Organizer: American Diabetes Association (ADA) 78th Scientific Sessions
  • Int'l Joint Research
• [Presentation] Unique profile of immune reconstruction after three types of HLA-mismatched allogeneic hematopoietic cell transplantations (2017)
  • Author(s): Shun Uemura, Yasuhiko Shibasaki, Takayuki Katagiri, Hiromi Ito, Tomoyuki Tanaka, Hironori Kobayashi, Takashi Ushiki, Kyoko Fuse, Miwako Narita, Hirohito Sone, Masayoshi Masuko
  • Organizer: JSH international symposium 2017
  • Place of Presentation: シーガイアコンベンションセンター（宮崎県宮崎市）
  • Year and Date: 2017-05-19
  • Int'l Joint Research
• [Presentation] Further prognostic factors for stratification of patients in the high-risk HCT-CI group undergoing allogeneic HCT (2017)
  • Author(s): Yasuhiko Shibasaki, Tatsuya Suwabe, Takayuki Katagiri, Tomoyuki Tanaka, Hironori Kobayashi, Kyoko Fuse, Takashi Ushiki, Miwako Narita, Hirohito Sone, Masayoshi Masuko
  • Organizer: American Society of Hematology annual meeting 2017
  • Int'l Joint Research
• [Presentation] Patient-Based Prediction Algorithm of Relapse after Allo-HSCT for Acute Leukemia Using Machine Learning Approach (2017)
  • Author(s): Kyoko Fuse, Shun Uemura, Tatsuya Suwabe,Takayuki Katagiri,Tomoyuki Tanaka,Takashi Ushiki, Yasuhiko Shibasaki, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Tastuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko
  • Organizer: American Society of Hematology annual meeting 2017
  • Int'l Joint Research
• [Presentation] Evaluation of Liver Iron Deposition in Transfusion-Dependent Patients By Dual-Energy CT (2016)
  • Author(s): Hironori Kobayashi, Norihiko Yoshimura, Takayuki Katagiri, Takashi Ushiki, Kyoko Fuse, Yasuhiko Shibasaki, Miwako Narita, Hirohito Sone, Masayoshi Masuko
  • Organizer: ASH annual meeting 2016
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] Elucidation of Tumor-Promoting Effects of Novel Adherent Immature Myeloid Cells in Tumor (2016)
  • Author(s): Takuya Tsubaki, Tetsuya Kadonosono, Tadashi Shiozawa, Takahiro Kuchimaru, Takashi Ushiki, Masayoshi Masuko, Shinae Kizaka-Kondoh
  • Organizer: ASH annual meeting 2016
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] The Predictive Factors of Favorable Prognosis after Allo-HSCT for Refractory Acute Leukemia (2016)
  • Author(s): Kyoko Fuse, Takayuki Katagiri, Yasuhiko Shibasaki, Tomoyuki Tanaka, Miwako Narita, Hirohito Sone, Masayoshi Masuko, Tatsuo Furukawa, Naoko Sato, Toshio Yano, Takashi Kuroha, Shigeo Hashimoto, Takashi Ushiki
  • Organizer: ASH annual meeting 2016
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] You have accessIntrabone Transplantation of a Single Cord Blood Unit Using Non-Irradiated Reduced-Intensity Conditioning (2016)
  • Author(s): Makoto Murata, Yoshinobu Maeda, Masayoshi Masuko, Nobuharu Fujii, Mitsune Tanimoto, Hironori Kobayashi, Yasuhiko Shibasaki, Ritsuro Suzuki, Tadashi Matsushita, Yoshihisa Kodera, Hitoshi Kiyoi, Tomoki Naoe, Tetsuya Nishida
  • Organizer: ASH annual meeting 2016
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Book] 白血病学（上） (2016)
  • Author(s): 布施香子、増子正義
  • Total Pages: 539
  • Publisher: 日本臨床
• [Remarks] 新潟大学医学部血液内分泌代謝内科研究紹介
  • URL: https://www.med.niigata-u.ac.jp/emh/research.html#tag_number04