Updated on 2021/06/10

写真a

 
Makoto Yoshimitsu
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Human and Environmental Science Associate Professor
Title
Associate Professor

Degree

  • 博士(医学) ( 2013.7   鹿児島大学 )

Research Interests

  • Hematology

Research Areas

  • Life Science / Hematology and medical oncology

Research History

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Human and Environmental Science   Associate Professor

    2019.4

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Center for Chronic Viral Diseases   Associate Professor

    2013.12 - 2019.3

  • Kagoshima University   Medical and Dental Hospital, Medical and Dental Sciences Area Medical and Dental Hospital Clinical Center Hematology, Endocrinology and Diabetology Center   Assistant Professor

    2013.4 - 2013.11

Professional Memberships

  • アメリカ血液学会

    2015.10

  • 日本人類遺伝学会

    2015.10

  • 日本リウマチ学会

    2015.10

  • 日本造血細胞移植学会

    2015.10

  • 日本血液学会

    2015.10

  • 日本内科学会

    2015.10

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Studying abroad experiences

  • 2002.4 - 2004.9   University Health Network  

Qualification acquired

  • Doctor

  • Specialist

  • Specialist

  • Specialist

  • Specialist

  • Attending physician

  • Authorized medicine

  • 日本血液学会代議員

  • 日本HTLV-1学会評議員

▼display all

 

Papers

  • Maruyama D. .  Randomised phase II study to optimise melphalan, prednisolone, and bortezomib in untreated multiple myeloma (JCOG1105) .  British Journal of Haematology192 ( 3 ) 531 - 541   2021.2Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:British Journal of Haematology  

    DOI: 10.1111/bjh.16878

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  • 吉満 誠 .  自家移植とbortezomib-melphalan-prednisone療法との比較試験(EMN02/HO95試験) .  血液内科82 ( 2 ) 241 - 245   2021.2自家移植とbortezomib-melphalan-prednisone療法との比較試験(EMN02/HO95試験)Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:(有)科学評論社  

  • Uchida Y. .  RLTPR Q575E: A novel recurrent gain-of-function mutation in patients with adult T-cell leukemia/lymphoma .  European Journal of Haematology106 ( 2 ) 221 - 229   2021.2Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:European Journal of Haematology  

    DOI: 10.1111/ejh.13540

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  • Yonekura K. .  Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study .  Blood Advances4 ( 20 ) 5133 - 5154   2020.10Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blood Advances  

    DOI: 10.1182/BLOODADVANCES.2020003053

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  • Aikawa A. .  Cell death induced by dorsomorphin in adult T-cell leukemia/lymphoma is AMPK-independent .  FEBS Journal287 ( 18 ) 4005 - 4015   2020.9Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:FEBS Journal  

    DOI: 10.1111/febs.15239

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  • Yokota R. .  Novel anti-CD70 antibody drug conjugate for the treatment of adult T-cell leukemia (ATL) .  Anticancer Research40 ( 8 ) 4471 - 4479   2020.8Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Anticancer Research  

    DOI: 10.21873/anticanres.14452

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  • 小代 彩, 井上 大栄, 鎌田 勇平, 藤野 聡司, 田淵 智久, 有馬 直佑, 内田 友一朗, 八幡 美保, 中村 大輔, 吉満 誠, 石塚 賢治 .  Mogamulizumabが奏効した著明な肝障害と胸腹水を伴う成人T細胞白血病・リンパ腫 .  臨床血液61 ( 6 ) 612 - 616   2020.6Mogamulizumabが奏効した著明な肝障害と胸腹水を伴う成人T細胞白血病・リンパ腫Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本血液学会-東京事務局  

    成人T細胞白血病・リンパ腫(ATL)はヒトTリンパ球向性ウイルスI型が原因となり発症する予後不良な末梢性T細胞腫瘍である。腫瘍浸潤による肝障害のため殺細胞性抗がん剤による化学療法が困難な状況をmogamulizumab(Moga)で救援し,長期寛解が得られている急性型ATLを報告する。症例は66歳男性,ATLの肝浸潤に伴う全身状態悪化のため減量化学療法を開始したが効果に乏しく,高ビリルビン血症,低アルブミン血症のため継続困難であった。Moga投与後,末梢血異常リンパ球は急速に減少,肝障害は改善し,通常量の化学療法が施行可能となった。抗体薬のMogaは体内薬物動態への肝代謝能や血清アルブミン値の影響が少ないと考えられ,肝浸潤による高ビリルビン血症や低アルブミン血症のため通常の殺細胞性抗がん剤を投与しにくい状態のATL患者の救援治療としても有望な選択肢である。(著者抄録)

  • Yoshimitsu M. .  Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors: Allo-HCT for ATL from HTLV-1 Antibody-Positive Donors .  Biology of Blood and Marrow Transplantation26 ( 4 ) 718 - 722   2020.4Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biology of Blood and Marrow Transplantation  

    DOI: 10.1016/j.bbmt.2019.12.004

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  • Nakamura D. .  Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area .  International Journal of Hematology111 ( 2 ) 234 - 240   2020.2Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Hematology  

    DOI: 10.1007/s12185-019-02769-w

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  • Shinohara A, Oshima K, Fuji S, Umeda K, Kako S, Kurokawa M, Tsukada N, Kasai M, Kondo T, Hashii Y, Nakamae H, Ikegame K, Kosaka Y, Shimada A, Nawa Y, Makoto Y, Yoshiko A, Fukuda T, Tanaka J, Ogata M .  Hematopoietic Stem Cell Transplantation in Solid Organ Recipients with Emphasis on Transplant Complications: A Nationwide Retrospective Survey on Behalf of the Japan Society for Hematopoietic Stem Cell Transplantation Transplant Complications Working Group. .  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation26 ( 1 ) 66 - 75   2020.1Hematopoietic Stem Cell Transplantation in Solid Organ Recipients with Emphasis on Transplant Complications: A Nationwide Retrospective Survey on Behalf of the Japan Society for Hematopoietic Stem Cell Transplantation Transplant Complications Working Group.Reviewed

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    DOI: 10.1016/j.bbmt.2019.08.021

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  • SHODAI Aya, YOSHIMITSU Makoto, ISHITSUKA Kenji, INOUE Hirosaka, KAMADA Yuhei, FUJINO Satoshi, TABUCHI Tomohisa, ARIMA Naosuke, UCHIDA Yuichiro, HACHIMAN Miho, NAKAMURA Daisuke .  Adult T-cell leukemia-lymphoma with severe hepatic damage and fluid retention successfully treated with mogamulizumab .  Rinsho Ketsueki61 ( 6 ) 612 - 616   2020Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Hematology  

    <p>Adult T-cell leukemia-lymphoma (ATL) is a peripheral T-cell malignancy caused by the human T-cell lymphotropic virus, type I and it has an extremely poor prognosis. A 66-year-old man with severe hepatic damage, massive pleural effusion and ATL cell infiltration-induced ascites was referred to our department. Reduced-intensity cytotoxic chemotherapy was attempted, but could not continue due to persistent hyperbilirubinemia. Laboratory results also showed elevated lactate dehydrogenase (LDH) and serum albumin levels were profoundly decreased. A humanized monoclonal antibody against chemokine receptor type 4 (CCR4), mogamulizumab (Moga), was thereby challenged and it successfully resolved the hepatic damage. Finally, a standard dose of chemotherapy could be administered, and it induced a complete remission. The patient is still in remission more than three years after the final dosage of standard chemotherapy. These results indicate that Moga, whose pharmacokinetics are not significantly influenced by hepatic function or serum albumin, could be a promising treatment option for patients with ATL complicated by severe hepatic damage due to infiltration of ATL cells.</p>

    DOI: 10.11406/rinketsu.61.612

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  • Kozako T. .  High expression of NAMPT in adult T-cell leukemia/lymphoma and anti-tumor activity of a NAMPT inhibitor .  European Journal of Pharmacology865   172738   2019.12Reviewed

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    DOI: 10.1016/j.ejphar.2019.172738

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  • Nakao S. .  Branch retinal artery occlusion in the untreated contralateral eye following aflibercept injections during heparin treatment: Possible contribution of a heparin-induced thrombocytopenia-like condition .  American Journal of Ophthalmology Case Reports16   100549   2019.12Reviewed

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    DOI: 10.1016/j.ajoc.2019.100549

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  • Yoshimitsu M. .  Essential thrombocytosis attributed to JAK2-T875N germline mutation .  International Journal of Hematology110 ( 5 ) 584 - 590   2019.11Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Hematology  

    DOI: 10.1007/s12185-019-02725-8

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  • Yoshimitsu M. .  A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia–lymphoma .  Bone Marrow Transplantation54 ( 8 ) 1266 - 1274   2019.8Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Bone Marrow Transplantation  

    DOI: 10.1038/s41409-018-0400-5

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  • 吉満 誠 .  ゴーシェ病の病態と治療 .  血液内科79 ( 2 ) 266 - 270   2019.8ゴーシェ病の病態と治療Reviewed

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  • Suzuki S. .  A survivin-responsive, conditionally replicating adenovirus induces potent cytocidal effects in adult T-cell leukemia/lymphoma .  BMC Cancer19 ( 1 ) 516   2019.5Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMC Cancer  

    DOI: 10.1186/s12885-019-5730-1

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  • 吉満 誠, 石塚 賢治 .  【リンパ腫・骨髄腫に対する免疫療法の現状と展望】成人T細胞白血病・リンパ腫に対する免疫チェックポイント阻害薬 .  血液内科78 ( 4 ) 460 - 464   2019.4【リンパ腫・骨髄腫に対する免疫療法の現状と展望】成人T細胞白血病・リンパ腫に対する免疫チェックポイント阻害薬Reviewed

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  • Kato K. .  The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation .  Hematological Oncology37 ( 1 ) 54 - 61   2019.2Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Hematological Oncology  

    DOI: 10.1002/hon.2558

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  • YOSHIMITSU Makoto .  Mature T- and NK-cell lymphomas:—deepening of genomic medicine and future prospects— .  Rinsho Ketsueki60 ( 5 ) 441 - 446   2019Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Hematology  

    <p>Mature T- and NK-cell neoplasms are a heterogeneous hematological malignancy. The current treatment of mature T- and NK-cell lymphoma depends on combination chemotherapy with or without auto/allogeneic hematopoietic stem cell transplantation. Recent comprehensive, integrated genetic analyses have revealed distinct genetic and molecular subgroups, which are related to different therapeutic responses. Thus, the genetic landscape of mature T- and NK-cell neoplasms is essential for the development of novel treatment modalities and offers opportunities for individualized therapy. This review aims to discuss the recent progress regarding genetic and molecular analyses of mature T- and NK-cell neoplasms toward stratified therapy.</p>

    DOI: 10.11406/rinketsu.60.441

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  • Hachiman M. .  In vitro effects of arsenic trioxide, interferon α and zidovudine in adult T cell leukemia/lymphoma cells .  Oncology Letters16 ( 1 ) 1305 - 1311   2018.7Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oncology Letters  

    DOI: 10.3892/ol.2018.8771

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  • Kozako T. .  The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells .  Oncotarget9 ( 45 ) 27645 - 27655   2018.6Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oncotarget  

    DOI: 10.18632/oncotarget.25291

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  • Kawajiri-Manako C. .  Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan .  Biology of Blood and Marrow Transplantation24 ( 6 ) 1180 - 1186   2018.6Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biology of Blood and Marrow Transplantation  

    DOI: 10.1016/j.bbmt.2018.01.026

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  • Yoshimitsu M. .  Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation .  Biology of Blood and Marrow Transplantation24 ( 4 ) 832 - 839   2018.4Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Biology of Blood and Marrow Transplantation  

    DOI: 10.1016/j.bbmt.2017.11.005

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  • Kataoka K. .  Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma .  Blood131 ( 2 ) 215 - 225   2018.1Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Blood  

    DOI: 10.1182/blood-2017-01-761874

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  • NAKAMURA Daisuke, HAYASHIDA Maiko, KUBOTA Kayoko, MATSUURA Eiji, TABUCHI Tomohisa, ARIMA Naosuke, INOUE Hirosaka, YOSHIMITSU Makoto, ISHITSUKA Kenji .  Successful treatment of POEMS syndrome-associated pulmonary hypertension with lenalidomide and dexamethasone therapy .  Rinsho Ketsueki59 ( 5 ) 489 - 491   2018Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Hematology  

    <p>POEMS syndrome is often complicated by pulmonary hypertension. The standard therapy for patients with POEMS syndrome is high-dose chemotherapy followed by autologous stem cell transplantation. However, the safety of high-dose chemotherapy for patients complicated with pulmonary hypertension remains unclear, and the optimal therapy for these patients is yet to be establishment. Herein, we report the case of a 54-year-old woman with POEMS syndrome accompanied by pulmonary hypertension. We successfully and safely performed lenalidomide and dexamethasone (Ld) therapy followed by high-dose chemotherapy and autologous stem cell transplantation, which improved her pulmonary hypertension. Thus, Ld can be considered as safe and effective for pulmonary hypertension with POEMS syndrome.</p>

    DOI: 10.11406/rinketsu.59.489

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  • 西馬場 理恵, 東 裕子, 藤井 一恭, 吉満 誠, 金蔵 拓郎 .  Myeloid sarcomaの1例 .  Skin Cancer32 ( 1 ) 12 - 15   2017.6Myeloid sarcomaの1例Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:(一社)日本皮膚悪性腫瘍学会  

    38歳、女性。初診の3ヵ月前から外陰部のしこりを自覚していた。徐々に増大してきたため近医を受診したところ、生検で悪性リンパ腫が疑われ、当院を紹介された。血液や骨髄には腫瘍細胞の浸潤は認められず、PET検査では陰部腫瘤のみ異常集積を認めた。病理組織検査では、真皮から脂肪織にかけてクロマチン濃染性で小型〜中型の不正核を有する腫瘍細胞の浸潤を認めた。免疫組織学的に腫瘍細胞はmyeloperoxidase、CD68、CD117に陽性であった。Myeloid sarcomaと診断し、急性骨髄性白血病に準じて、治療を行った。化学療法、放射線治療、末梢血幹細胞移植が行われたが、病状は進行し、発症から3年後に永眠した。(著者抄録)

  • 吉満 誠 .  【成人T細胞白血病リンパ腫(ATL)研究と診療の進歩】ATLに対する化学療法とモガムリズマブの効果 .  血液内科74 ( 3 ) 346 - 351   2017.3【成人T細胞白血病リンパ腫(ATL)研究と診療の進歩】ATLに対する化学療法とモガムリズマブの効果Reviewed

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  • 中村 桃子, 保坂 加奈子, 秋元 正樹, 吉満 誠, 大坪 秀雄, 石塚 賢治 .  アバタセプト投与中に免疫不全関連リンパ増殖性疾患を再発した関節リウマチの1例 .  九州リウマチ37 ( 1 ) 67 - 71   2017.3アバタセプト投与中に免疫不全関連リンパ増殖性疾患を再発した関節リウマチの1例Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:九州リウマチ学会  

    68歳男性。1991年関節リウマチ(RA)と診断、メトトレキサート(MTX)を開始、2004年インフリキシマブ(IFX)が追加された。2013年に縦隔・腹腔内にリンパ節腫大を認め医原性免疫不全関連リンパ増殖性疾患(OIIA-LPD)を疑い、MTXとIFXを中止し自然退縮した。RAの悪化を認め、免疫抑制剤が追加されたが副作用で中止となり、2014年1月アバタセプト(ABT)単独療法開始、2年後、sIL-2Rの上昇と縦隔リンパ節腫大からOIIA-LPDと診断した。ABTの中止のみでLPDは退縮したが、消化管大量出血による出血性ショックと播種性血管内凝固症候群のため死亡した。病理解剖で残存していた縦隔リンパ節はEBV陽性ホジキンリンパ腫と診断された。OIIA-LPD寛解後のRAの治療においてABTは比較的安全との症例報告が散見されるが、ABTでもLPDを誘発する可能性があり、注意が必要である。(著者抄録)

  • Dworski S. .  Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy .  Biochimica et Biophysica Acta - Molecular Basis of Disease1863 ( 2 ) 386 - 394   2017.2Reviewed

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    DOI: 10.1016/j.bbadis.2016.11.031

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  • Kubo T. .  Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy .  Journal of Cardiology69 ( 1 ) 302 - 307   2017.1Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Cardiology  

    DOI: 10.1016/j.jjcc.2016.05.014

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  • Yoshimitsu M, Hachiman M, Uchida Y, Arima N, Arai A, Kamada Y, Shide K, Ito M, Shimoda K, Ishitsuka K. .  Essential thrombocytosis attributed to JAK2-T875N germline mutation. .  International Journal of Hematology110 ( 5 ) 584 - 590   2019.8Essential thrombocytosis attributed to JAK2-T875N germline mutation. Reviewed

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: doi: 10.1007/s12185-019-02725-8.

  • Ishida T, Jo T, Takemoto S, Suzushima H, Suehiro Y, Choi I, Yoshimitsu M, Saburi Y, Nosaka K, Utsunomiya A, Kobayashi Y, Yamamoto K, Fujiwara H, Ishitsuka K, Yoshida S, Taira N, Imada K, Kato K, Moriuchi Y, Yoshimura K, Takahashi T, Tobinai K, Ueda R. .  Follow-up of a randomised phase II study of chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: impact on allogeneic haematopoietic stem cell transplantation. .  British Journal of Haematology184 ( 3 ) 479 - 483   2019.2Follow-up of a randomised phase II study of chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: impact on allogeneic haematopoietic stem cell transplantation.Reviewed

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    DOI: doi: 10.1111/bjh.15123.

  • Yoshimitsu M, Utsunomiya A, Fuji S, Fujiwara H, Fukuda T, Ogawa H, Takatsuka Y, Ishitsuka K, Yokota A, Okumura H, Ishii K, Nishikawa A, Eto T, Yonezawa A, Miyashita K, Tsukada J, Tanaka J, Atsuta Y, Kato K; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation. .  A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. .  Bone Marrow Transplantation   2018.12A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma.Reviewed

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)  

    DOI: doi: 10.1038/s41409-018-0400-5.

  • Kato K, Uike N, Wake A, Yoshimitsu M, Tobai T, Sawayama Y, Takatsuka Y, Fukuda T, Uchida N, Eto T, Nakashima Y, Kondo T, Taguchi J, Miyamoto T, Nakamae H, Ichinohe T, Kato K, Suzuki R, Utsunomiya A; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation. .  The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation. .  Hematological Oncology   2018.9The outcome and characteristics of patients with relapsed adult T cell leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation.Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: doi: 10.1002/hon.2558.

  • Kozako T, Sato K, Uchida Y, Kato N, Aikawa A, Ogata K, Kamimura H, Uemura H, Yoshimitsu M, Ishitsuka K, Higaki Y, Tanaka H, Honda SI, Soeda S. .  The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells. .  Oncotarget9 ( 45 ) 27645 - 27655   2018.6The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells.Reviewed

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: doi: 10.18632/oncotarget.25291.

  • Kawajiri-Manako C, Sakaida E, Ohwada C, Miyamoto T, Azuma T, Taguchi J, Mori T, Hasegawa Y, Kondo T, Yujiri T, Yoshimitsu M, Imada K, Kurahashi S, Kahata K, Ichinohe T, Hirokawa M, Atsuta Y, Nakaseko C. .  Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan. .  Biol Blood Marrow Transplant24 ( 6 ) 1180 - 1186   2018.6Efficacy and Long-Term Outcomes of Autologous Stem Cell Transplantation in POEMS Syndrome: A Nationwide Survey in Japan.Reviewed

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    POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.

  • Yoshimitsu M, Tanosaki R, Kato K, Ishida T, Choi I, Takatsuka Y, Fukuda T, Eto T, Hidaka M, Uchida N, Miyamoto T, Nakashima Y, Moriuchi Y, Nagafuji K, Miyazaki Y, Ichinohe T, Takanashi M, Atsuta Y, Utsunomiya A; ATL Working Group of the Japan Society for Hematopoietic Cell Transplantation. .  Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation. .  Biol Blood Marrow Transplant24 ( 4 ) 832 - 839   2018.4Risk Assessment in Adult T Cell Leukemia/Lymphoma Treated with Allogeneic Hematopoietic Stem Cell Transplantation.Reviewed

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    Disease status at allogeneic hematopoietic cell transplantation (HCT) is an important pretransplant prognostic factor of HCT in adult T cell leukemia/lymphoma (ATL); however, other prognostic factors, including comorbidities, were not predictive in small cohort analyses. Several scoring systems (HCT-specific comorbidity index [HCT-CI]/modified European Group for Blood and Marrow Transplantation risk score [mEBMT]) have been adopted to predict HCT outcomes in other hematologic malignancies. We retrospectively evaluated HCT-CI and mEBMT to predict nonrelapse mortality (NRM) in 824 ATL patients registered in the Japan Society for Hematopoietic Cell Transplantation TRUMP database, from 2008 until 2013. A higher HCT-CI was associated with greater NRM when comparing HCT-CI 0 versus HCT-CI 1 to 3 and HCT-CI 0 versus HCT-CI ≥ 4. A higher mEBMT score was not associated with higher NRM when comparing mEBMT 0 to 3 with 4 to 6. Because ATL patients are older and consequently at risk of additional complications, we developed an optimized prognostic index for ATL (ATL-HCT-PI) using known risk factors: age, HCT-CI, and donor-recipient sex combination. The ATL-HCT-PI scores effectively predicted the 2-year NRM (22.0%, 27.7%, and 44.4%, respectively). Therefore, the newly developed ATL-HCT-PI, in combination with other risk factors, is more useful for predicting NRM in HCT for ATL patients.

    DOI: doi: 10.1016/j.bbmt.2017.11.005.

  • Kataoka K, Iwanaga M, Yasunaga JI, Nagata Y, Kitanaka A, Kameda T, Yoshimitsu M, Shiraishi Y, Sato-Otsubo A, Sanada M, Chiba K, Tanaka H, Ochi Y, Aoki K, Suzuki H, Shiozawa Y, Yoshizato T, Sato Y, Yoshida K, Nosaka K, Hishizawa M, Itonaga H, Imaizumi Y, Munakata W, Shide K, Kubuki Y, Hidaka T, Nakamaki T, Ishiyama K, Miyawaki S, Ishii R, Nureki O, Tobinai K, Miyazaki Y, Takaori-Kondo A, Shibata T, Miyano S, Ishitsuka K, Utsunomiya A, Shimoda K, Matsuoka M, Watanabe T, Ogawa S. .  Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma. .  Blood131 ( 2 ) 215 - 225   2018.1Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma.Reviewed

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    Adult T-cell leukemia/lymphoma (ATL) is a heterogeneous group of peripheral T-cell malignancies characterized by human T-cell leukemia virus type-1 infection, whose genetic profile has recently been fully investigated. However, it is still poorly understood how these alterations affect clinical features and prognosis. We investigated the effects of genetic alterations commonly found in ATL on disease phenotypes and clinical outcomes, based on genotyping data obtained from 414 and 463 ATL patients using targeted-capture sequencing and single nucleotide polymorphism array karyotyping, respectively. Aggressive (acute/lymphoma) subtypes were associated with an increased burden of genetic and epigenetic alterations, higher frequencies of TP53 and IRF4 mutations, and many copy number alterations (CNAs), including PD-L1 amplifications and CDKN2A deletions, compared with indolent (chronic/smoldering) subtypes. By contrast, STAT3 mutations were more characteristic of indolent ATL. Higher numbers of somatic mutations and CNAs significantly correlated with worse survival. In a multivariate analysis incorporating both clinical factors and genetic alterations, the Japan Clinical Oncology Group prognostic index high-risk, older age, PRKCB mutations, and PD-L1 amplifications were independent poor prognostic factors in aggressive ATL. In indolent ATL, IRF4 mutations, PD-L1 amplifications, and CDKN2A deletions were significantly associated with shorter survival, although the chronic subtype with unfavorable clinical factors was only marginally significant. Thus, somatic alterations characterizing aggressive diseases predict worse prognosis in indolent ATL, among which PD-L1 amplifications are a strong genetic predictor in both aggressive and indolent ATL. ATL subtypes are further classified into molecularly distinct subsets with different prognosis. Genetic profiling might contribute to improved prognostication and management of ATL patients.

    DOI: doi: 10.1182/blood-2017-01-761874

  • Casey N, Fujiwara H, Azuma T, Murakami Y, Yoshimitsu M, Masamoto I, Nawa Y, Yamanouchi J, Narumi H, Yakushijin Y, Hato T, Yasukawa M. .  An unusual, CD4 and CD8 dual-positive, CD25 negative, tumor cell phenotype in a patient with adult T-cell leukemia/lymphoma. .  Leukemia Lymphoma   2018An unusual, CD4 and CD8 dual-positive, CD25 negative, tumor cell phenotype in a patient with adult T-cell leukemia/lymphoma.Reviewed

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    DOI: doi: 10.1080/10428194.2018.1439168.

  • Nakamura D, Hayashida M, Kubota K, Matsuura E, Tabuchi T, Arima N, Inoue H, Yoshimitsu M, Ishitsuka K. .  Successful treatment of POEMS syndrome-associated pulmonary hypertension with lenalidomide and dexamethasone therapy .  Rinsho Ketsueki59 ( 5 ) 489 - 491   2018Successful treatment of POEMS syndrome-associated pulmonary hypertension with lenalidomide and dexamethasone therapyReviewed

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    DOI: doi: 10.11406/rinketsu.59.489.

  • Hachiman M, Yoshimitsu M, Ezinne C, Kuroki A, Kozako T, Arima N .  In vitro effects of arsenic trioxide, interferon α and zidovudine in adult T cell leukemia/lymphoma cells. .  Oncology Letter16 ( 1 ) 1305 - 1311   2018In vitro effects of arsenic trioxide, interferon α and zidovudine in adult T cell leukemia/lymphoma cells.Reviewed

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    DOI: doi: 10.3892/ol.2018.8771

  • Tokunaga M, Yonekura K, Nakamura D, Haraguchi K, Tabuchi T, Fujino S, Hayashida M, Maekawa K, Arai A, Nakano N, Kamada Y, Kubota A, Inoue H, Owatari S, Takeuchi S, Takatsuka Y, Otsuka M, Hanada S, Matsumoto T, Yoshimitsu M, Ishitsuka K, Utsunomiy A. .  Clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma. .  British Journal of Haematology   2017.4Clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma.Reviewed

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    DOI: 10.1111/bjh.14634.

  • Dworski S, Lu P, Khan A, Maranda B, Mitchell JJ, Parini R, Di Rocco M, Hugle B, Yoshimitsu M, Magnusson B, Makay B, Arslan N, Guelbert N, Ehlert K, Jarisch A, Gardner-Medwin J, Dagher R, Terreri MT, Lorenco CM, Barillas-Arias L, Tanpaiboon P, Solyom A, Norris JS, He X, Schuchman EH, Levade T, Medin JA. .  Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy. .  Biochim Biophys Acta1863 ( 2 ) 386 - 394   2017.2Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy. Reviewed

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  • Kubo T, Ochi Y, Baba Y, Hirota T, Tanioka K, Yamasaki N, Yoshimitsu M, Higuchi K, Takenaka T, Nakajima K, Togawa T, Tsukimura T, Sano S, Tei C, Sakuraba H, Kitaoka H. .  Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy. .  Journal of Cardiology69 ( 1 ) 302 - 307   2017.1Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy. Reviewed

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  • Ishida T, Fujiwara H, Nosaka K, Taira N, Abe Y, Imaizumi Y, Moriuchi Y, Jo T, Ishizawa K, Tobinai K, Tsukasaki K, Ito S, Yoshimitsu M, Otsuka M, Ogura M, Midorikawa S, Ruiz W, Ohtsu T .  Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002. .  Jounal of Clinical Oncolgy34 ( 34 ) 4086 - 4093   2016.12Multicenter Phase II Study of Lenalidomide in Relapsed or Recurrent Adult T-Cell Leukemia/Lymphoma: ATLL-002.Reviewed

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    Purpose Few treatment options exist for adult T-cell leukemia/lymphoma (ATL), and the prognosis for this disease is poor. A phase I study of lenalidomide demonstrated preliminary antitumor activity in patients with relapsed ATL. The current phase II study evaluated the efficacy and safety of lenalidomide monotherapy in patients with relapsed or recurrent ATL. Patients and Methods Patients 20 years of age or older with acute, lymphoma, or unfavorable chronic subtype ATL, who had received one or more prior anti-ATL systemic chemotherapy and achieved stable disease or better on their last anti-ATL therapy with subsequent relapse or recurrence, were eligible. Patients received oral lenalidomide 25 mg/d continuously until disease progression or unacceptable toxicity. The primary end point was overall response rate; secondary end points included safety, tumor control rate (stable disease or better), time to response, duration of response, time to progression, progression-free survival, and overall survival. Results Objective responses were noted in 11 of 26 patients (overall response rate, 42%; 95% CI, 23% to 63%), including four complete responses and one unconfirmed complete response. The tumor control rate was 73%. The median time to response and duration of response were 1.9 months and not estimable, respectively, and the median time to progression was 3.8 months. The median progression-free survival and overall survival were 3.8 and 20.3 months, respectively. The most frequent grade ≥ 3 adverse events were neutropenia (65%), leukopenia (38%), lymphopenia (38%), and thrombocytopenia (23%), which were all manageable and reversible. Conclusion Lenalidomide demonstrated clinically meaningful antitumor activity and an acceptable toxicity profile in patients with relapsed or recurrent aggressive ATL, hinting at its potential to become a treatment option. Further investigations of lenalidomide in ATL and other mature T-cell neoplasms are warranted.

  • Maeda K, Ding Q, Yoshimitsu M, Kuwahata T, Miyazaki Y, Tsukasa K, Hayashi T, Shinchi H, Natsugoe S, Takao S. .  CD133 Modulate HIF-1α Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells. .  International Journal of Molecular Sciences17 ( 7 )   2016.6CD133 Modulate HIF-1α Expression under Hypoxia in EMT Phenotype Pancreatic Cancer Stem-Like Cells. Reviewed

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  • Miyazaki Y, Matsubara S, Ding Q, Tsukasa K, Yoshimitsu M, Kosai K, Takao S .  Efficient elimination of pancreatic cancer stem cells by hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition. .  Molecular Cancer15 ( 1 ) 49   2016.6Efficient elimination of pancreatic cancer stem cells by hedgehog/GLI inhibitor GANT61 in combination with mTOR inhibition.Reviewed

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  • Kozako T, Soeda S, Yoshimitsu M, Arima N, Kuroki A, Hirata S, Tanaka H, Imakyure O, Tone N, Honda S, Soeda S. .  Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. .  FEBS Open Bio6 ( 5 ) 442 - 460   2016.4Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells. Reviewed

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  • Kusano S, Yoshimitsu M, Hachiman M, Ikeda M. .  I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions. .  Virology486   219 - 227   2015.12I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions. Reviewed

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    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability.

  • Nakamura D, Yoshimitsu M, Kuroki A, Hachiman M, Kamada Y, Ezinne CC, Arai A, Inoue H, Hamada H, Hayashida M, Suzuki S, Fujino S, Arima N, Arima M, Tabuchi T, Okada S, Arima N. .  A new ATL xenograft model and evaluation of pyrrolidine dithiocarbamate as a potential ATL therapeutic agent. .  Experimental Hematology43 ( 11 ) 944 - 950   2015.11A new ATL xenograft model and evaluation of pyrrolidine dithiocarbamate as a potential ATL therapeutic agent. Reviewed

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    Adult T-cell leukemia/lymphoma (ATL) is caused by human T-lymphotrophic virus type 1 infection and is one of the most refractory malignant T-cell lymphomas. Improvement of ATL therapy options requires the establishment of appropriate ATL animal models. In this study, we successfully generated an ATL mouse model by xenotransplantation of primary peripheral blood mononuclear cells (PBMCs) isolated from ATL patients (ATL cells) into nonobese diabetic/severe combined immunodeficiency/Jak3-null mice (NOJ mice). To generate the model, the ATL S1T cell line was subcutaneously injected into mice. Primary ATL cells were then transplanted subcutaneously, intraperitoneally, or intravenously. ATL cells infiltrated multiple organs, and elevated human soluble interleukin 2 receptor (IL-2R) levels were detected in peripheral blood. Injection of one million primary ATL cells was needed for successful engraftment into host mice. Thawed cells, frozen long-term in liquid nitrogen, could also be transplanted; however, more cells were required to achieve similar results. The median mouse survival time was proportional to the number of cells injected. Successful secondary transplantation of ATL cells from one NOJ mouse into another was achieved and confirmed by T-cell receptor analysis. Finally, we examined the effects of the antioxide pyrrolidine dithiocarbamate (PDTC) as an antitumor agent in vivo. PDTC administration inhibited the increase of soluble IL-2R and improved mouse survival, suggesting that this compound has potential as an anti-ATL agent. We demonstrated that ATL cells could be stably xenotransplanted into NOJ mice using primary cells. This model will be useful in the establishment of novel therapies to treat ATL.

  • Ishitsuka K, Utsunomiya A, Katsuya H, Takeuchi S, Takatsuka Y, Hidaka M, Sakai T, Yoshimitsu M, Ishida T, Tamura K. .  A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma. .  Cancer Science106 ( 9 ) 1219 - 1223   2015.9A phase II study of bortezomib in patients with relapsed or refractory aggressive adult T-cell leukemia/lymphoma. Reviewed

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    Adult T-cell leukemia/lymphoma (ATL) is a malignancy of peripheral T-lymphocytes with a poor prognosis. This multicenter, two-stage, single-arm, phase II study assessed the efficacy and safety of bortezomib in patients with relapsed/refractory ATL who received at least one regimen of chemotherapy. The primary endpoint was the best overall response rate (ORR), and secondary endpoints included safety, the best response by lesions, and progression-free survival (PFS). Fifteen patients were enrolled in the first stage of this study. One partial remission (PR) and five stable disease (SD) were observed as the best overall responses, and ORR was 6.7% (95% confidence interval (C.I.) 0.17-31.95%). Responses according to disease sites were one complete remission (CR) in peripheral blood, two PR in measurable targeted lesions, and two PR in skin lesions. Progression-free survival (PFS) was 38 (95% CI; 18-106) days. All patients developed ≥1 adverse events (AEs), and 80% of patients had ≥1 grade 3/4 AEs; however, no new safety findings were obtained. Although these results fulfilled the planned settings to proceed to the second stage, the coordinating committee decided to terminate this study because single agent activity did not appear to be very promising for this cohort of patients.

  • Kozako T, Suzuki T, Yoshimitsu M, Uchida Y, Kuroki A, Aikawa A, Honda S, Arima N, Soeda S. .  Novel small-molecule SIRT1 inhibitors induce cell death in adult T-cell leukaemia cells. .  Scientific Report19 ( 5 ) 11345   2015.6Novel small-molecule SIRT1 inhibitors induce cell death in adult T-cell leukaemia cells.Reviewed

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  • Dworski S, Berger A, Furlonger C, Moreau JM, Yoshimitsu M, Trentadue J, Au BC, Paige CJ, Medin JA. .  Markedly perturbed hematopoiesis in acid ceramidase deficient mice. .  Haematologica   2015.2Markedly perturbed hematopoiesis in acid ceramidase deficient mice. Reviewed

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  • Kawada H, Yoshimitsu M, Nakamura D, Arai A, Hayashida M, Kamada Y, Maekawa K, Fujino S, Arima M, Arima N, Tabuchi T, Inoue H, Hamda H, Suzuki S, Matsushita K, and Arima N. .  A retrospective analysis of treatment outcomes in aggressive adult T cell leukemia/lymphoma patients treated with or without allogeneic stem cell transplantation: A single center experience. .  Biology of Blood and Marrow Transplantation. ( 21 ) 696 - 700   2015.2 A retrospective analysis of treatment outcomes in aggressive adult T cell leukemia/lymphoma patients treated with or without allogeneic stem cell transplantation: A single center experience.Reviewed

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  • Kameda T, Shide, Yamaji T, Kamiunten A, Sekine M, Taniguchi Y, Hidaka T, Kubuki Y, Shimoda H, Marutsuka K, Sashida G, Aoyama K, Yoshimitsu M, Harada T, Abe H, Miike T, Iwakiri H, Tahara Y, Sueta,M, Yamamoto S, Hasuike S, Nagata K, Iwama A, Kitanaka A, and Shimoda K. .  Loss-of-TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator. .  Blood ( 125 ) 304 - 315   2015.1 Loss-of-TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.Reviewed

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  • Ezinne CC, Yoshimitsu M, Arima N. .  CD160 expression defined a uniquely exhausted subset of T lymphocytes in HTLV-1 infection. .  Biochem Biophys Res Commun.453   379 - 384   2014.11 CD160 expression defined a uniquely exhausted subset of T lymphocytes in HTLV-1 infection. Reviewed

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  • Ezinne CC, Yoshimitsu M, White Y, Arima N. .  HTLV-1 Specific CD8+ T Cell Function Augmented by Blockade of 2B4/CD48 Interaction in HTLV-1 Infection. .  PLoS One.5 ( 9 )   2014.2HTLV-1 Specific CD8+ T Cell Function Augmented by Blockade of 2B4/CD48 Interaction in HTLV-1 Infection.Reviewed

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  • Ding Q, Miyazaki Y, Tsukasa K, Matsubara S, Yoshimitsu M, Takao S .  CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis. .  Molecular Cancer27   2014.1CD133 facilitates epithelial-mesenchymal transition through interaction with the ERK pathway in pancreatic cancer metastasis.Reviewed

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  • White Y, Yoshimitsu M, Kozako T, Matsushita K, Koriyama C, Uozumi K, Suzuki S, Kofune H, Arima N .  Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 (HTLV-1) infection. .  Leukemia Lymphoma   2013.3Effects of exogenous interleukin-7 on CD8(+) T-cell survival and function in human T-cell lymphotropic virus type 1 (HTLV-1) infection.Reviewed

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  • Nakmura D, Yoshimitsu M, Kawada H, Inoue H, Kuroki T, Kaieda T, Fujino S, Hamada H, Suzuki S, Matsushita K, Uozumi K, Arima N .  Recombinant human soluble thrombomodulin for the treatment of hepatic sinusoidal obstructive syndrome post allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation .  Bone Marrow Transplantation47 ( 3 ) 463 - 464   2012.3Recombinant human soluble thrombomodulin for the treatment of hepatic sinusoidal obstructive syndrome post allogeneic hematopoietic stem cell transplantation. Bone Marrow TransplantationReviewed

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  • Pacienza N, Yoshimitsu M, Mizue N, Au BCY, Wang JCM, Fan X, Takenaka T, Medin JA. .  Lentivector transduction improves outcomes over transplantation of human HSCs alone in NOD/SCID/Fabry mice .  Molecular Therapy   2012.3Lentivector transduction improves outcomes over transplantation of human HSCs alone in NOD/SCID/Fabry miceReviewed

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  • Ding Q, Yoshimitsu M, Kuwahata T, Maeda K, Hayashi T, Obara T, Miyazaki Y, Matsubara S, Natsugoe S, Takao S. .  Establishment of a highly migratory subclone reveals that CD133 contributes to migration and invasion through epithelial-mesenchymal transition in pancreatic cancer .  Hum Cell25 ( 1 ) 1 - 8   2012.3Establishment of a highly migratory subclone reveals that CD133 contributes to migration and invasion through epithelial-mesenchymal transition in pancreatic cancerReviewed

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  • Kozako T, Aikawa A, Shoji T, Fujimoto T, Yoshimitsu M, Shirasawa S, Tanaka H, Honda SI, Shimeno H, Arima N, Soeda S. .  High expression of the longevity gene product SIRT1, and apoptosis induction by sirtinol in adult T-cell leukemia cells. .  International Journal of Cancer   2012.2High expression of the longevity gene product SIRT1, and apoptosis induction by sirtinol in adult T-cell leukemia cells.Reviewed

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  • Maekawa K, Yoshimitsu M, Fujiwara H, Matsushita K, Kawada H, Hamada H, Suzuki S, Uozumi K, Ohtsuka M, Hanada S, Yabe M, Yabe H and N Arima. .  Successful allo-HSCT with a minimal myeloablative conditioning regimen in an adult patient with Fanconi’s anemia .  Bone Marrow Transplantation47 ( 1 ) 159 - 160   2012.1Successful allo-HSCT with a minimal myeloablative conditioning regimen in an adult patient with Fanconi’s anemiaReviewed

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  • Kozako T, Arima N, Yoshimitsu M, Honda S-I, Soeda S .  Liposomes and Nanotechnology in drug development: focus on oncotargets .  International Journal of nanomedicine ( 7 ) 4943 - 4951   2012Liposomes and Nanotechnology in drug development: focus on oncotargetsReviewed

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  • White Y, Hamada T, Yoshimitsu M, Nakashima M, Hachiman M, Kozako T, Matsushita K, Uozumi K, Suzuki S, Kofune H, Furukawa T and Arima N 2011 (12) 4251-4257. .  Novel Cytotoxic Isolated from Jamaican Hyptis verticillata jacq Induces Apoptosis and Overcomes Multidrug Resistance .  Anticancer Research31 ( 12 ) 4251 - 4257   2011.12 Novel Cytotoxic Isolated from Jamaican Hyptis verticillata jacq Induces Apoptosis and Overcomes Multidrug ResistanceReviewed

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  • Tomohiro Kozako, Makoto Yoshimitsu, Masaki Akimoto, YohannWhite, Kakushi Matsushita, Shinji Soeda, Hiroshi Shimeno, RyujiKubota, Shuji Izumo, Naomichi Arima .  PD-1/PD-L1 Pathway-Mediated Immune Responses against HumanT-Lymphotropic Virus Type I in HAM/TSP and Carriers withAutoimmune Disorders .  Human Immunology72 ( 11 ) 1001 - 1006   2011.11PD-1/PD-L1 Pathway-Mediated Immune Responses against HumanT-Lymphotropic Virus Type I in HAM/TSP and Carriers withAutoimmune DisordersReviewed

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  • Makoto Yoshimitsu , Koji Higuchi , Xin Fan , Sonshin Takao, Jeffrey A. Medin, Chuwa Tei , Toshihiro Takenaka .  Sequencing and characterization of the porcine ・-galactosidse A gene: Towards the generation of a porcine model for Fabry disease .  Molecular Biology Report38 ( 5 ) 3145-52   2011.6Sequencing and characterization of the porcine ・-galactosidse A gene: Towards the generation of a porcine model for Fabry diseaseReviewed

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  • Makoto Yoshimitsu, KojiHiguchi, MasaakiMiyata, Sean Devine, AndreMattman, SandraSirrs, Jeffrey A.Medin, ChuwaTei, ToshihiroTakenaka .  Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: pitfalls of mutation analyses in patients with low α-galactosidase A activity .  Journal of Cardiology57 ( 3 ) 345 - 353   2011.5Identification of novel mutations in the α-galactosidase A gene in patients with Fabry disease: pitfalls of mutation analyses in patients with low α-galactosidase A activityReviewed

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  • Koji Higuchi, Makoto Yoshimitsu, Xin Fan, Xiaoxin Guo, Vanessa I Rasaiah, Jennifer Yen, Chuwa Tei, Toshihiro Takenaka, Jeffrey A Medin .  α-Galactosidase A-Tat Fusion Enhances Storage Reduction inHearts and Kidneys of Fabry Mice .  Molecular Medicine16 ( 42130 ) 216 - 221   2010.5α-Galactosidase A-Tat Fusion Enhances Storage Reduction inHearts and Kidneys of Fabry MiceReviewed

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  • Yoshimitsu M (co-first author), Kozako T, Fujiwara H, Masamoto I, Horai S, White Y, Akimoto M, Suzuki S, Matsushita K, Uozumi K, Tei C, Arima N .  PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patients .  Leukemia23   375 - 382   2009.2PD-1/PD-L1 expression in human T-cell leukemia virus type 1 carriers and adult T-cell leukemia/lymphoma patientsReviewed

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  • Yoshimitsu M, Fujiwara F, Ozaki A, Hamada H, Matsushita K, Arima N and Tei C. .  Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions. .  International Journal of Hematology88   331 - 335   2008.8Case of a patient with Philadelphia-chromosome-positive acute lymphoblastic leukemia relapsed after myeloablative allogeneic hematopoietic stem cell transplantation treated successfully with imatinib and sequential donor lymphocyte infusions. Reviewed

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  • Inoue H, Matsushita K, Arima N, Hamada H, Uozumi K, Ozaki A, Akimoto M, Kawada H, Kukita T, Yoshimitsu M, Matsumoto T, Tei C. .  High prevalence of human T-lymphotropic virus type I carriers among patients with myelodysplastic syndrome refractory anemia with excess of blasts (RAEB), RAEB in transformation and acute promyelocytic leukemia. .  Leuk Lymphoma49 ( 2 ) 315 - 321   2008.2High prevalence of human T-lymphotropic virus type I carriers among patients with myelodysplastic syndrome refractory anemia with excess of blasts (RAEB), RAEB in transformation and acute promyelocytic leukemia.Reviewed

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  • Akimoto M, Kozako T, Sawada T, Matsushita K, Ozaki A, Hamada H, Kawada H, Yoshimitsu M, Tokunaga M, Haraguchi K, Uozumi K, Arima N, Tei C. .  Anti-HTLV-1 tax antibody and tax-specific cytotoxic T lymphocyte are associated with a reduction in HTLV-1 proviral load in asymptomatic carriers. .  J Med Virol79 ( 7 ) 977 - 986   2007.7Anti-HTLV-1 tax antibody and tax-specific cytotoxic T lymphocyte are associated with a reduction in HTLV-1 proviral load in asymptomatic carriers.Reviewed

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  • Makoto Yoshimitsu (Co-first author), Shobha Ramsubirand Jeffrey A. Medin .  Anti-CD25 targeted killing of bicistronically transduced cells: a novel safety mechanism against retroviral genotoxicity. .  Molecular Therapy15 ( 6 ) 1174 - 1181   2007.6Anti-CD25 targeted killing of bicistronically transduced cells: a novel safety mechanism against retroviral genotoxicity.Reviewed

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  • Sheng-Ben Liang, Makoto Yoshimitsu, Armando Poeppl, Vanessa I. Rasaiah, Jianhui Cai, Daniel H. Fowler, and Jeffrey A. Medin .  Multiple reduced-intensity conditioning regimens facilitate correction of Fabry mice after transplantation of transduced cells. .  Molecular Therapy15 ( 3 ) 618 - 627   2007.3Multiple reduced-intensity conditioning regimens facilitate correction of Fabry mice after transplantation of transduced cells.Reviewed

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  • Yoshimitsu M, Higuchi K, Ramsubir S, Nonaka T, Rasaiah VI, Siatskas C, Liang S-B, Murray GJ, Brady RO and Medin JA .  Efficient correction of Fabry mice and patient cells mediated by lentiviral transduction of hematopoietic stem/progenitor cells. .  Gene Therapy14 ( 3 ) 256 - 265   2007.2Efficient correction of Fabry mice and patient cells mediated by lentiviral transduction of hematopoietic stem/progenitor cells.Reviewed

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  • Makoto Yoshimitsu, Koji Higuchi, Fayez Dawood, Vanessa I. Rasaiah, Bilal Ayach, Manyin Chen, Peter liu, Jeffrey A. Medin .  Correction of cardiac abnormalities in Fabry mice by direct intraventricular injection of a recombinant lentiviral vector that engineers expression of alpha-galactosidase A .  Circulation Journal70 ( 11 ) 1503 - 1508   2006.11Correction of cardiac abnormalities in Fabry mice by direct intraventricular injection of a recombinant lentiviral vector that engineers expression of alpha-galactosidase AReviewed

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  • Bilal Ayach, Makoto Yoshimitsu, Fayez Dawood, Mei Sun, Sara Arab, Manyin Chen, Koji Higuchi, Christopher Siatskas, Paul Lee, Hilda Lim, Jane Zhang, Eva Cukerman, William L. Stanford, Jeffrey A. Medin, Peter P. Liu. .  Stem Cell Factor Receptor Induces Progenitor and Natural Killer Cell Mediated Cardiac Survival and Repair Post-Myocardial Infarction. .  Proc Natl Acad Sci USA103 ( 7 ) 2304 - 2309   2006.2Stem Cell Factor Receptor Induces Progenitor and Natural Killer Cell Mediated Cardiac Survival and Repair Post-Myocardial Infarction.Reviewed

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  • Fujiwara H, Kawada H, Matsushita K, Hamada H, Ozaki A, Inoue H, Yoshimitsu M, Kukita T, Arimura K, Ohtsubo H, Uozumi K, Arima N, Tei C .  Case of a patient with progressive adult T-cell leukemia/lymphoma treated successfully by reduced-intensity conditioning stem cell transplantation from an HLA-incompatible related donor. .  Int J Hematol82 ( 4 ) 357 - 361   2005.11Case of a patient with progressive adult T-cell leukemia/lymphoma treated successfully by reduced-intensity conditioning stem cell transplantation from an HLA-incompatible related donor.Reviewed

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  • Yoshimitsu M, Sato T, Tao K, Walia JS, Rasaiah VI, Sleep GT, Murray GJ, Poeppl AG, Underwood J, West L, Brady RO, Medin JA. .  Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors .  Proc Natl Acad Sci USA101 ( 48 ) 16909 - 16914   2004.11Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectorsReviewed

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Books

  • Prevention of Human T-Cell Lymphotropic Virus Infection and Adult T-Cell Leukemia.

    Yoshimitsu M, Kozako T, Arima N( Role: Joint author)

    T-Cell Leukemia - Characteristics, Treatment and Prevention  2013 

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    Language:English Book type:Scholarly book

  • Transduction and Post-Translational Events in Gene Therapy Targeting Hematopoietic Stem Cells

    Christopher Siatskas, Makoto Yoshimitsu, and Jeffrey A. Medin( Role: Joint author)

    Focus on Fabry Disease. Focus on stem cell research (editor Erik V. Greer) Chapter VII:by Nova Biomedical Books. Hauppauge, New York USA  2004.1 

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    Language:English Book type:Scholarly book

MISC

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Presentations

  • 42. Yoshimitsu M, Tanosaki R, Kato K, Ishida T, Choi I, Fukuda T, Takatsuka Y, Eto T, Uchida N, Moriuchi Y, Nagamura-Inoue T, Mori S, Sakamaki H, Atsuta Y, Utsunomiya A.   Risk Stratification of Outcomes Among Patients with Adult T-Cell Leukemia/Lymphoma Receiving Allogeneic Hematopoietic Cell Transplantation: A Retrospective Analysis of the JSHCT ATL Working Group.   International conference

    Tandem BMT meeting.  Tandem BMT meeting.

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    Event date: 2015.2

    Language:English  

    Venue:San Diego, CA, USA  

    国際学会

  • 41. Kawajiri C, Sakaida E, Ohwada C, Miyamoto T, Azuma T, Taguchi J, Mori T, Hasegawa Y, Kondo T, Yujiri T, Yoshimitsu M, Tsudo M, Iwasaki T, Shigematsu A, Suzuki R, Atsuta Y, Hirokawa M, Sakamaki H, and Nakaseko C.   The Efficacy and Long-Term Outcomes of ASCT in POEMS Syndrome: A Multicenter Retrospective Study in Japan.   International conference

    56th Annual Meeting and Exposition of the American Society of Hematology.  56th Annual Meeting and Exposition of the American Society of Hematology.

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    Event date: 2014.12

    Language:English  

    Venue: San Francisco, CA, USA  

    国際学会

  • Hachiman M, Yoshimitsu M, Kuroki A, Nakamura D, Arima N.   In vitro and in vivo effect of ATO/IFN/AZT for adult T cell leukemia/lymphoma.   International conference

    19th Congress of European Hematology Association.  19th Congress of European Hematology Association.

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    Event date: 2014.6

    Language:English  

    Venue:Milan, Italy  

    国際学会

  • Yoshimitsu M   A case of newly diagnosed acute type ATL treated with the combination of arsenic trioxide, pegylated interferon, and zidovudine.   International conference

    T Cell Lymphoma Forum  T Cell Lymphoma Forum

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    Event date: 2013.1

    Language:English  

    Venue:San Francisco, CA, USA  

    国際学会

  • 吉満誠、Yohann White、新元淳子、 黒木綾子、Ezinne C. Chibueze、川田英明、鈴木紳介、松下格司、魚住公治、有馬直道   HTLV-Iキャリア及びATLL患者細胞におけるPD-L1発現の検討  

    日本血液学会  日本血液学会

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    Event date: 2011.10

    Language:Japanese  

    Venue:名古屋  

    国内学会

  • 吉満 誠、小迫知弘、藤原 弘 、政元いずみ、鈴木紳介、松下格司、魚住公治、鄭 忠和、有馬直道   成人T細胞白血病リンパ腫におけるPD-1/PD-L1経路の関与の検討  

    日本血液学会・日本臨床血液学会合同総会  日本血液学会・日本臨床血液学会合同総会

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    Event date: 2007.10

    Language:Japanese  

    Venue:神奈川  

    国内学会

  • 吉満誠、小迫 知弘、藤原 弘、政元 いずみ、安崎 和博、尾崎 厚夫、松下 格司、魚住 公治、有馬 直道、鄭 忠和   ATLL患者での抗HTLV-I Tax特異的CTLの機能低下におけるPD-1/PD-L1経路の関与の検討  

    日本血液学会・臨床血液学会合同総会  日本血液学会・臨床血液学会合同総会

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    Event date: 2006.10

    Language:Japanese  

    Venue:福岡  

    国内学会

  • 吉満誠, 藤原 弘, 政元 いずみ, 小迫 知弘, 尾崎 厚夫, 青木 則子, 川田 英明, 松下 格司, 有馬 直道, 鄭 忠和   同種造血幹細胞移植後移植片対ATL効果に於ける抗HTLV-I Tax CTLの臨床床的意義  

    日本内科学会総会  日本内科学会総会

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    Event date: 2006.4

    Language:Japanese  

    Venue:横浜  

    国内学会

  • 吉満誠、藤原弘   ATLLに対する移植免疫応答  

    第一回 免疫治療研究会  第一回 免疫治療研究会

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    Event date: 2006.3

    Language:Japanese  

    Venue:松山  

    研究会

  • Makoto Yoshimitsu, MD, Christpher Siatskas, PhD, Sheng-Ben Liang, MD, PhD, Vanessa I Rasaiah, Koji Higuchi, MD, Gary J Murray, PhD, Toshihiro Takenaka, MD, PhD, Chuwa Tei, MD, PhD, Roscoe O Brady, MD and Jeffrey A Medin, PhD   Long-term and Sustained Correction of the -Galactosidase A Deficiency in Fabry Mice and Patient Cells Receiving Lentivirally Transduced Hematopoietic Stem/Progenitor Cells   International conference

    47th ASH annual meeting  47th ASH annual meeting

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    Event date: 2005.12

    Language:English  

    Venue:Atlanta  

    国際学会

  • Makoto Yoshimitsu, Christopher Siatskas, Sheng-Ben Liang, Vanessa I Rasaiah, Armando G Poeppl, Koji Higuchi, Shobha Ramsubir, Toshihiro Takenaka, Gary J Murray, Chuwa Tei, Roscoe O Brady, Jeffrey A Medin   Long-term and Sustained Correction in Hearts of Fabry Mice Receiving Lentivirally Transduced Hematopoietic Stem/Progenitor Cells   International conference

    Scientific sessions 2005 American Heart Association  Scientific sessions 2005 American Heart Association

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    Event date: 2005.11

    Language:English  

    Venue:Dallas  

    国際学会

  • 吉満誠 竹中俊宏 樋口公嗣 Jeffrey A Medin 鄭忠和   心Fabry病の遺伝子治療:レンチウイルスベクターを用いた検討  

    日本心臓病学会  日本心臓病学会

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    Event date: 2005.9

    Language:Japanese  

    Venue:大阪  

    国内学会

  • Yoshimitsu M, Takenaka T, Higuchi K, Ostuji Y, MEdin JA and Tei C.   Gene therapy for cardiac fabry disease using a lentiviral vector.   International conference

    The 8th State of the art circulation forum in tokyo  The 8th State of the art circulation forum in tokyo

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    Event date: 2005.8

    Language:English  

    Venue:Tokyo  

    国際学会

  • Yoshimitsu M, Ramsubir S, Sleep G, Medin JA   In vivo clearance of transduced cells using an anti-CD25-saporin immunotoxin following therapeutic retroviral gene transfer   International conference

    3rd University Health Network Research Day  3rd University Health Network Research Day

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    Event date: 2004.11

    Language:English  

    Venue:Toronto  

    国際学会

  • Yoshimitsu M, Tao K, Sato T, Murray GJ, West L, Brady RO, Medin JA   Long-term Expression of Human ??-Galactosidase A in Fabry Mice by Neonatal Lentiviral Gene Transfer   International conference

    The American Society of Human Genetics, 54th ASGH Annual Meeting  The American Society of Human Genetics, 54th ASGH Annual Meeting

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    Event date: 2004.10

    Language:English  

    Venue:Toronto  

    国際学会

  • Yoshimitsu M, Tao K, Fan X, West L, Medin JA   Neonatal Gene Therapy with a Single Lentiviral Vector Injection Results in Therapeutic Levels of ??-Galactosidase A Correction in Fabry Mice   International conference

    The American Society of Gene Therapy 7th Annual Meeting  The American Society of Gene Therapy 7th Annual Meeting

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    Event date: 2004.6

    Language:English  

    Venue:Minneapolis  

    国際学会

  • Yoshimitsu M, Tao K, Fan X, West L, Medin JA   Sustained therapeutic levels of ??-galactosidase A in Fabry mice by neonatal lentivirus gene transfer   International conference

    3rd Annual Southern Ontario Gene Therapy Meeting  3rd Annual Southern Ontario Gene Therapy Meeting

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    Event date: 2004.5

    Language:English  

    Venue:London  

    国際学会

  • Yoshimitsu M, Tao K, Fan X, West L, Medin JA   Sustained therapeutic levels of ??-galactosidase A in Fabry mice by neonatal lentivirus gene transfer.   International conference

    1st International Conference on Glycoprotein & Related Storage Diseases Glycoproteinoses:An International Workshop on Advances in Pathogenesis and Therapy  1st International Conference on Glycoprotein & Related Storage Diseases Glycoproteinoses:An International Workshop on Advances in Pathogenesis and Therapy

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    Event date: 2004.4

    Language:English  

    Venue:Washington DC  

    国際学会

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Research Projects

  • CARD11を標的とした成人T細胞白血病リンパ腫に対する創薬基盤の樹立

    2017.12 - 2018.11

    民間財団等  内藤記念科学奨励金・研究助成  

    吉満誠、原博満 河原康一

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    Grant type:Competitive

    成人T細胞白血病・リンパ腫(ATL)はHTLV-1ウイルスによって引き起こされる極めて難治性造血器悪性腫瘍である。現在の標準治療は抗がん剤ないしは抗体薬を併用した化学療法が中心であるが、その生存期間中央値は8.3-10.6か月と極めて短い。同種造血幹細胞移植の導入により長期生存症例を認めるようになったが、治療関連死亡率は3割以上にのぼり、また患者集団の半数以上をしめる65歳以上の高齢者では、移植療法はその毒性から制限され、非侵襲的な新規治療法の開発が急務である。

    近年網羅的遺伝子変異解析により、ATLを含めた非ホジキンリンパ腫に共通の遺伝子変異が複数報告されている。同定された変異遺伝子群は機能獲得型変異もあり、これを標的とした治療法開発は有望であると考える。ATLにおいて同定された変異遺伝子はT細胞受容体刺激経路の分子(図1)に蓄積しており、その中でもPLCG1/PRKCB/CARD11は機能獲得型変異によるNFkBの恒常的活性化をきたすことで腫瘍化の維持に関与していると考えられた。 当講座でのエクソーム解析においてもPLCG1/PRKCB/CARD11の変異はATL症例の約8割程度(図2)で認められた。PLCG1とPRKCBはCARD11を活性化することでNFkBの活性化をきたすことから、今回CARD11の活性化阻害剤を開発することを目的として本研究を立案した。共同研究者の原らはB細胞リンパ腫においてCARD11の機能獲得型変異がNFkBの活性化をきたす機序として、CARD11のSH3ドメインとGUKドメインのシス型・トランス型の会合が必須であることを報告した(図3)。本研究では特にCARD11のSH3ドメインとGUKドメインの会合阻害剤(first in class)の開発を目指す。