研究室概要

造血器（骨髄）、血管、血液、脾臓・胸腺・リンパ節などの組織は生体内で極めて緻密なネットワークを形成し、生命活動を維持するために極めて重要な役割を演じています。血液は採取しやすく、試験管内でも扱いやすいことから、早くから研究対象として用いられてきました。現在、私たちの血液・腫瘍内科学教室では、細胞生物学から、生化学、遺伝子工学、分子生物学，創薬に至るまでの様々な手法を駆使して、目の前の患者さんの病態を解明し、新規治療法を開発・確立することを使命として日夜研究に取り組んでいます。特に、白血病、悪性リンパ腫発症に関わる分子メカニズムの解析や新規分子標的療法の開発、分子標的薬に対する薬剤耐性の克服、同種造血幹細胞移植療法の成績向上のための移植免疫の研究など、多岐にわたる最先端の研究分野で成果をあげてきています。
さて当教室は、旧内科学第一講座の血液グループが独立したものです。旧内科学第一講座の創設は大正時代で、日本血液学会創始者として知られる勝沼精蔵先生が初代教授を務められました。その後、日比野進先生、祖父江逸郎先生、齋藤英彦先生、直江知樹先生が歴任され、これまでに血液学のみならず内科学全般においても歴史と伝統のある教室として発展を遂げてきました。附属病院では「血液内科」を担当し、造血器腫瘍（白血病、リンパ腫、骨髄腫など）、造血障害（再生不良性貧血など）、凝固異常症（血友病、von Willebrand病など）などの診療に取り組んでいます。現在教室には博士課程14名の大学院生が在籍しており、卒後は海外留学を希望する人も多く、現在2名が海外留学中です。また、現医局員24名のうち7名が海外留学経験者です。また、海外からの留学生も、随時受け入れています。

研究プロジェクト

血液・腫瘍内科学は、国内外の研究室とも密接な連携を取りながら、主に以下のテーマについての研究を積極的に推し進めています。

1. 臨床研究グループ　（早川文彦教授（保健学科）、村田誠准教授、西田徹也講師、島田和之講師、寺倉精太郎病院講師、石川裕一助教、川島直実助教、西脇聡史病院講師（先端医療開発部）、鍬塚八千代病院助教（先端医療開発部）、牛島洋子病院助教（卒後臨床研修・キャリア形成支援センター）、葉名尻良医員）
   当科では臨床治験、多施設共同臨床研究に積極的に参加し造血器疾患における治療法の確立に取り組んでいます。JALSG（日本成人白血病治療共同研究グループ）、JCOG（日本臨床腫瘍研究グループ）に参加し、白血病、骨髄異形成症候群、悪性リンパ腫、多発性骨髄腫などの造血器悪性腫瘍に対する臨床研究を通じてこれらの治療成績の向上を目指しています。また、造血幹細胞移植に関しては、名古屋BMTグループの一員として多施設共同研究や日本造血細胞移植学会を通じて全国規模の後方視的研究なども行っています。
2. 分子病態解明・標的治療開発グループ（早川文彦教授（保健学科）、島田和之講師、石川裕一助教、川島直実助教、牛島洋子病院助教（卒後臨床研修・キャリア形成支援センター））
   急性白血病、骨髄異形成症候群、悪性リンパ腫の病態の解明、新規治療法の開発を行っています。次世代シーケンサーを用いた網羅的遺伝子解析及び各種オミクス解析、Patient-derived xenograft（PDX:患者腫瘍細胞を異種移植したマウスモデル）の作成と解析などを通じて、患者さんの臨床像とその背景にある分子機構を明らかにし、より高い効果を持つ治療法の研究、治療薬に対する耐性化機序の解明を目指しています。また製薬企業と共同で、新たな分子標的治療薬の前臨床開発も行っています。
3. 免疫細胞療法開発グループ　（村田誠准教授、西田徹也講師、寺倉精太郎病院講師、葉名尻良医員）
   GVHDやウイルス感染などの移植後合併症の克服やGVL効果を高めるための研究、キメラ抗原受容体などの遺伝子治療の開発のための研究などに取り組んでいます。さらに、「骨髄内臍帯血移植」「間葉系幹細胞を用いた移植」「ウイルス抗原特異的CTL療法」などの臨床研究を通じて新たな移植免疫療法の開発を目指しています。
4. 血栓・止血グループ（松下正教授（輸血部）、鈴木伸明助教（輸血部）、兼松毅病院助教（検査部））
   先天性、後天性の出血性疾患及び血栓性素因の病態研究を進めています。ヒト検体を用いた研究のみでなく、von Willebrand病、MYH9異常症、プロトロンビン異常症などでは、ヒトから得た知見を元にオリジナルのマウスモデル作製と、その解析に取り組んでいます。

教員

構成員名	役職	所属
清井 仁	教授	血液・腫瘍内科学
村田 誠	准教授	血液・腫瘍内科学
西田 徹也	講師	血液・腫瘍内科学
島田 和之	講師	血液・腫瘍内科学
寺倉 精太郎	病院講師	血液・腫瘍内科学
石川 裕一	助教	血液・腫瘍内科学
川島 直実	助教	血液・腫瘍内科学
牛島 洋子	病院助教（卒後臨床研修・キャリア形成支援センター）	卒後臨床研修・キャリア形成支援センター 血液腫瘍内科学

研究実績

• 2018年

  1. Hattori H, Ishikawa Y, Kawashima N, Akashi A, Yamaguchi Y, Harada Y, Hirano D, Adachi Y, Miyao K, Ushijima Y, Terakura S, Nishida T, Matsushita T, Kiyoi H. Identification of the novel deletion-type PML-RARA mutation associated with the retinoic acid resistance in acute promyelocytic leukemia. PLoS One. 2018:13:e0204850
  2. Shimada K, Hayakawa F, Kiyoi H. Biology and management of primary effusion lymphoma. Blood. 2018:132:1879-1888.
  3. Seto A, Atsuta Y, Kawashima N, Ozawa Y, Miyamura K, Kiyoi H. Impact of hospital length of stay on the risk of readmission and overall survival after allogeneic stem cell transplantation. Int J Hematol. 2018:108:290-297
  4. Ueda N, Uemura Y, Zhang R, Kitayama S, Iriguchi S, Kawai Y, Yasui Y, Tatsumi M, Ueda T, Liu TY, Mizoro Y, Okada C, Watanabe A, Nakanishi M, Senju S, Nishimura Y, Kuzushima K, Kiyoi H, Naoe T, Kaneko S. Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response. Stem Cell Reports. 2018:10:1935-1946.
  5. Goto T, Murata M, Terakura S, Nishida T, Adachi Y, Ushijima Y, Shimada K, Ishikawa Y, Hayakawa F, Nishio N, Nishiwaki S, Hirakawa A, Kato K, Takahashi Y, Kiyoi H. Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells: A clinical study protocol. Medicine (Baltimore).2018:97:e0449.
  6. Miyao K, Terakura S, Okuno S, Julamanee J, Watanabe K, Hamana H, Kishi H, Sakemura R, Koyama D, Goto T, Nishida T, Murata M, Kiyoi H. Introduction of Genetically Modified CD3ζ Improves Proliferation and Persistence of Antigen-Specific CTLs. Cancer Immunol Res. 2018:6:733-744.
  7. Nishiyama T, Ishikawa Y, Kawashima N, Akashi A, Adachi Y, Hattori H, Ushijima Y, Kiyoi H. Mutation analysis of therapy-related myeloid neoplasms. Cancer Genetics. 2018;222-223:38-45.
  8. Harada Y, Nagata Y, Kihara R, Ishikawa Y, Asou N, Ohtake S, Miyawaki S, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kobayashi S, Kitamura K, Sakaida E, Onizuka M, Takeshita A, Ishida F, Suzushima H, Ishizawa K, Naoe T, Matsumura I, Miyazaki Y, Ogawa S, Kiyoi H; Japan Adult Leukemia Study Group JALSG. Prognostic analysis according to the 2017 ELN risk stratification by genetics in adult acute myeloid leukemia patients treated in the Japan Adult Leukemia Study Group (JALSG) AML201 study. Leuk Res. 2018;66:20-27.
  9. Yamaura T, Nakatani T, Uda K, Ogura H, Shin W, Kurokawa N, Saito K, Fujikawa N, Date T, Takasaki M, Terada D, Hirai A, Akashi A, Chen F, Adachi Y, Ishikawa Y, Hayakawa F, Hagiwara S, Naoe T, Kiyoi H. A novel irreversible FLT3 inhibitor, FF-10101, shows excellent efficacy against AML cells with FLT3 mutations. Blood. 2018;131:426-438.
  10. Kuwatsuka Y, Tomizawa D, Kihara R, Nagata Y, Shiba N, Iijima-Yamashita Y, Shimada A, Deguchi T, Miyachi H, Tawa A, Taga T, Kinoshita A, Nakayama H, Kiyokawa N, Saito AM, Koh K, Goto H, Kosaka Y, Asou N, Ohtake S, Miyawaki S, Miyazaki Y, Sakura T, Ozawa Y, Usui N, Kanamori H, Ito Y, Imai K, Suehiro Y, Kobayashi S, Kitamura K, Sakaida E, Ogawa S, Naoe T, Hayashi Y, Horibe K, Manabe A, Mizutani S, Adachi S, Kiyoi H. Prognostic value of genetic mutations in adolescent and young adults with acute myeloid leukemia. Int J Hematol.2018;107:201-210.

• 2017年

  1. Adachi Y, Ishikawa Y, Kiyoi H. Identification of volasertib-resistant mechanism and evaluation of combination effects with volasertib and other agents on acute myeloid leukemia. Oncotarget 2017;8:78452-78465.
  2. Kojima Y, Hayakawa F, Morishita T, Sugimoto K, Minamikawa Y, Iwase M, Yamamoto H, Hirano D, Imoto N, Shimada K, Okada S, Kiyoi H. YM155 induces apoptosis through proteasome-dependent degradation of MCL-1 in primary effusion lymphoma. Pharmacol Res. 2017;120:242-251.
  3. Terakura S, Kuwatsuka Y, Yamasaki S, Wake A, Kanda J, Inamoto Y, Mizuta S, Yamaguchi T, Uchida N, Kouzai Y, Aotsuka N, Ogawa H, Kanamori H, Nishiwaki K, Miyakoshi S, Onizuka M, Amano I, Fukuda T, Ichinohe T, Atsuta Y, Murata M, Teshima T. GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia. Bone Marrow Transplant. 2017;52:1261-1267
  4. Murata M, Maeda Y, Masuko M, Onishi Y, Endo T, Terakura S, Ishikawa Y, Iriyama C, Ushijima Y, Goto T, Fujii N, Tanimoto M, Kobayashi H, Shibasaki Y, Fukuhara N, Inamoto Y, Suzuki R, Kodera Y, Matsushita T, Kiyoi H, Naoe T, Nishida T. Phase II study of intrabone single unit cord blood transplantation for hematological malignancies. Cancer Sci. 2017;108:1634-1639
  5. Kawashima N, Terakura S, Nishiwaki S, Koyama D, Ozawa Y, Ito M, Miyamura K. Increase of bone marrow macrophages and CD8(+) T lymphocytes predict graft failure after allogeneic bone marrow or cord blood transplantation. Bone Marrow Transplant. 2017;52:1164-1170
  6. Terakura S, Wake A, Inamoto Y, Murata M, Sakai R, Yamaguchi T, Takahashi S, Uchida N, Onishi Y, Ohashi K, Ozawa Y, Kanamori H, Yamaguchi H, Fukuda T, Ichinohe T, Takanashi M, Atsuta Y, Teshima T. Exploratory research for optimal GvHD prophylaxis after single unit CBT in adults: short-term methotrexate reduced the incidence of severe GvHD more than mycophenolate mofetil. Bone Marrow Transplant. 2017;52:423-430.
  7. Murata M, Ikegame K, Morishita Y, Ogawa H, Kaida K, Nakamae H, Ikeda T, Nishida T, Inoue M, Eto T, Kubo K, Sakura T, Mori T, Uchida N, Ashida T, Matsuhashi Y, Miyazaki Y, Ichinohe T, Atsuta Y, Teshima T. Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GVHD: an analysis of the JSHCT. Bone Marrow Transplant. Bone Marrow Transplant. 2017;52:252-257.
  8. Aoki T, Shimada K, Sakamoto A, Sugimoto K, Morishita T, Kojima Y, Shimada S, Kato S, Iriyama C, Kuno S, Harada Y, Tomita A, Hayakawa F, Kiyoi H. Emetine elicits apoptosis of intractable B-cell lymphoma cells with MYC rearrangement through inhibition of glycolytic metabolism. Oncotarget. 2017;8:13085-13098.
  9. Suzuki N, Hirakawa A, Kishimoto M, Kanematsu T, Ogawa M, Kiyoi H, Matsushita T. Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study. Haemophilia. 2017;23:215-221.
  10. Nishiwaki S, Sugiura I, Miyata Y, Saito S, Sawa M, Nishida T, Miyamura K, Kuwatsuka Y, Kohno A, Yuge M, Kasai M, Iida H, Kurahashi S, Osaki M, Goto T, Terakura S, Murata M, Nishikawa H, Kiyoi H. Efficacy and safety of autologous peripheral blood stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia: A study protocol for a multicenter exploratory prospective study (Auto-Ph17 study). Medicine (Baltimore). 2017;96:e9568.
  11. Koyama D, Murata M, Hanajiri R, Okuno S, Kamoshita S, Julamanee J, Takagi E, Hirano D, Miyao K, Sakemura R, Goto T, Hayakawa F, Seto A, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H. High incidence of extensive chronic graft-versus-host disease in patients with the REG3A rs7588571 non-GG genotype. PLoS One. 2017;12:e0185213.
  12. Shirahata-Adachi M, Iriyama C, Tomita A, Suzuki Y, Shimada K, Kiyoi H. Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome. Leuk Res. 2017; 63: 90-97.

• 2016年

  1. Goto T, Nishida T, Takagi E, Miyao K, Koyama D, Sakemura R, Hanajiri R, Watanabe K, Imahashi N, Terakura S, Murata M, Kiyoi H. Programmed Death-Ligand 1 on Antigen-presenting Cells Facilitates the Induction of Antigen-specific Cytotoxic T Lymphocytes: Application to Adoptive T-Cell Immunotherapy. J Immunother, 2016 Oct;39(8):306-15.
  2. Suzuki N, Hirakawa A, Kishimoto M, Kanematsu T, Ogawa M, Kiyoi H, Matsushita T. Retrospective analysis of in vivo recovery and clearance during continuous infusion of recombinant factor VIII products: a single-institution study. Haemophilia, 2016.Oct.
  3. Takagi Y, Shimada K, Shimada S, Sakamoto A, Naoe T, Nakamura S, Hayakawa F, Tomita A, Kiyoi H. SPIB is a novel prognostic factor in diffuse large B-cell lymphoma that mediates apoptosis via the PI3K-AKT pathway. Cancer Sci, 2016 Sep;107(9):1270-80.
  4. Suzuki Y, Tomita A, Nakamura F, Iriyama C, Shirahata-Adachi M, Shimada K, Akashi A, Ishikawa Y, Kaneda N, Kiyoi H. Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes. Cancer Sci, 2016 Sep;107(9):1329-37.
  5. Niwa Y, Minami Y, Abe A, Hayakawa F, Yamada K, Naoe T. Wnt signaling is associated with cell survival in the interaction between acute myeloid leukemia cells and stromal cells. Leuke lymphoma,2016 Sep;57(9):2192-4.
  6. Morishita T, Hayakawa F, Sugimoto K, Iwase M, Yamamoto H, Hirano D, Kojima Y, Imoto N, Naoe T, Kiyoi H. The photosensitizer verteporfin has light-independent anti-leukemic activity for Ph-positive acute lymphoblastic leukemia and synergistically works with dasatinib. Oncotarget, 2016.Aug.
  7. Sakemura R, Terakura S, Watanabe K, Julamanee J, Takagi E, Miyao K, Koyama D, Goto T, Hanajiri R, Nishida T, Murata M, Kiyoi H. A Tet-On Inducible System for Controlling CD19-Chimeric Antigen Receptor Expression upon Drug Administration. Cancer Immunol Res, 2016 Aug;4(8):658-68.
  8. Fukushima N, Minami Y, Kakiuchi S, Kuwatsuka Y, Hayakawa F, Jamieson C, Kiyoi H, Naoe T. Small-molecule Hedgehog inhibitor attenuates the leukemia-initiation potential of acute myeloid leukemia cells. Cancer Sci, 2016.Jul.
  9. Shimada K, Shimada S, Sugimoto K, Nakatochi M, Suguro M, Hirakawa A, Hocking TD, Takeuchi I, Tokunaga T, Takagi Y, Sakamoto A, Aoki T, Naoe T, Nakamura S, Hayakawa F, Seto M, Tomita A, Kiyoi H. Development and analysis of patient derived xenograft mouse models in intravascular large B-cell lymphoma. Leukemia, 2016 Jul;30(7):1568-79.
  10. Inagaki Y, Hayakawa F, Hirano D, Kojima Y, Morishita T, Yasuda T, Naoe T, Kiyoi H. PAX5 tyrosine phosphorylation by SYK co-operatively functions with its serine phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism for antigen-triggered plasma cell differentiation. Biochem Biophys Res Commun, 2016 Jun;475(2):176-81.
  11. Chen F, Ishikawa Y, Akashi A, Naoe T, Kiyoi H. Co-expression of wild-type FLT3 attenuates the inhibitory effect of FLT3 inhibitor on FLT3 mutated leukemia cells. Oncotarget, 2016 Jun.
  12. Yasuda T, Tsuzuki S, Kawazu M, Hayakawa F, Kojima S, Ueno T, Imoto N, Kohsaka S, Kunita A, Doi K, Sakura T, Yujiri T, Kondo E, Fujimaki K, Ueda Y, Aoyama Y, Ohtake S, Takita J, Sai E, Taniwaki M, Kurokawa M, Morishita S, Fukayama M, Kiyoi H, Miyazaki Y, Naoe T, Mano H. Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults. Nat Genet, 2016 May;48(5):569-74.
  13. Imoto N, Hayakawa F, Kurahashi S, Morishita T, Kojima Y, Yasuda T, Sugimoto K, Tsuzuki S, Naoe T, Kiyoi H. BLNK is a selective target of repression by PAX5-PML in the differentiation block that leads to the development of acute lymphoblastic leukemia. J Biol Chem, 2016 Feb;291(9):4723-31.
  14. Terakura S, Atsuta Y, Tsukada N, Kobayashi T, Tanaka M, Kanda J, Najima Y, Fukuda T, Uchida N, Takahashi S, Nagamura-Inoue T, Morishima Y, Miyamura K; Japan Society for Hematopoietic Cell Transplantation. Comparison of Outcomes of 8/8 and 7/8 Allele-Matched Unrelated Bone Marrow Transplantation and Single-Unit Cord Blood Transplantation in Adults with Acute Leukemia. Biol Blood Marrow Transplant, 2016 Feb;22(2):330-8.
  15. Kishimoto M, Suzuki N, Murata M, Ogawa M, Kanematsu T, Takagi A, Kiyoi H, Kojima T, Matsushita T. The first case of antithrombin-resistant prothrombin Belgrade mutation in Japanese. Ann Hematol, 2016 Feb;95(3):541-2.
  16. Kanematsu T, Suzuki N, Yoshida T, Kishimoto M, Aoki T, Ogawa M, Kagami Y, Kiyoi H, Matsushita T, Kunishima S. A case of MYH9 disorders caused by a novel mutation (p.K74E). Ann Hematol, 2016 Jan;95(1):161-3.
  17. Miyao K, Sawa M, Kuwatsuka Y, Ozawa Y, Kato T, Kohno A, Sao H, Nishida T, Iida H, Naito K, Tsurumi H, Taji H, Mizuta S, Kusumoto S, Nakase K, Morishita Y, Kawashima N, Miyamura K, Murata M. Influence of melphalan plus fludarabine- conditioning regimen in elderly patients aged ≥ 55 years with hematological malignancies. Bone Marrow Transplant, 2016 Jan;51(1):157-60.

• 2015年

  1. Aoki T, Shimada K, Suzuki R, Izutsu K, Tomita A, Maeda Y, Takizawa J, Mitani K, Igarashi T, Sakai K, Miyazaki K, Mihara K, Ohmachi K, Nakamura N, Takasaki H, Kiyoi H, Nakamura S, Kinoshita T, Ogura M. High-dose chemotherapy followed by autologous stem cell transplantation for relapsed/refractory primary mediastinal large B-cell lymphoma. Blood Cancer J, 2015 Dec;5:e372.
  2. Hanajiri R, Murata M, Sugimoto K, Murase M, Sakemura R, Goto T, Watanabe K, Imahashi N, Terakura S, Ohashi H, Akatsuka Y, Kurahashi S, Miyamura K, Kiyoi H, Nishida T, Naoe T. Integration of humoral and cellular HLA-specific immune responses in cord blood allograft rejection. Bone Marrow Transplant, 2015 Sep;50(9):1187-94.
  3. Suzuki N, Takedani H, Hirakawa A, Ushijima Y, Matsushita T. The features of clearance in recombinant factor IX (BeneFIX(®)). Haemophilia. 2015 Sep;21(5):702-7.
  4. Sugimoto K, Hayakawa F, Shimada S, Morishita T, Shimada K, Katakai T, Tomita A, Kiyoi H, Naoe T. Discovery of a drug targeting microenvironmental support for lymphoma cells by screening using patient-derived xenograft cells. Sci Rep, 2015 Aug;5:13054.
  5. Imahashi N, Ohashi H, Terakura S, Miyao K, Sakemura R, Kato T, Sawa M, Yokohata E, Kurahashi S, Ozawa Y, Nishida T, Kiyoi H, Watamoto K, Kohno A, Kasai M, Kato C, Iida H, Naoe T, Miyamura K, Murata M; for the Nagoya Blood and Marrow Transplantation Group. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse. Ann Hematol, 2015 Jul;94(7):1139-48.
  6. Imahashi N, Nishida T, Goto T, Terakura S, Watanabe K, Hanajiri R, Sakemura R, Imai M, Kiyoi H, Naoe T, Murata M. Simple and Efficient Generation of Virus-specific T Cells for Adoptive Therapy Using Anti-4-1BB Antibody. J Immunother, 2015 Feb-Mar;38(2):62-70.
  7. Watanabe K, Terakura S, Martens AC, van Meerten T, Uchiyama S, Imai M, Sakemura R, Goto T, Hanajiri R, Imahashi N, Shimada K, Tomita A, Kiyoi H, Nishida T, Naoe T, Murata M. Target Antigen Density Governs the Efficacy of Anti-CD20-CD28-CD3 ζ Chimeric Antigen Receptor-Modified Effector CD8+ T Cells. J Immunol, 2015 Feb;194(3): 911-20.

• 2014年

  1. Aoki T, Izutsu K, Suzuki R, Nakaseko C, Arima H, Shimada K, Tomita A, Sasaki M, Takizawa J, Mitani K, Igarashi T, Maeda Y, Fukuhara N, Ishida F, Niitsu N, Ohmachi K, Takasaki H, Nakamura N, Kinoshita T, Nakamura S, Ogura M. Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan. Haematologica, 2014 Dec;99(12):1817-25.
  2. Hayakawa F, Sakura T, Yujiri T, Kondo E, Fujimaki K, Sasaki O, Miyatake J, Handa H, Ueda Y, Aoyama Y, Takada S, Tanaka Y, Usui N, Miyawaki S, Suenobu S, Horibe K, Kiyoi H, Ohnishi K, Miyazaki Y, Ohtake S, Kobayashi Y, Matsuo K, Naoe T; Japan Adult Leukemia Study Group (JALSG). Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. Blood Cancer J, 2014 Oct;4:e252.
  3. Kishimoto M, Matsuda T, Yanase S, Katsumi A, Suzuki N, Ikejiri M, Takagi A, Ikawa M, Kojima T, Kunishima S, Kiyoi H, Naoe T, Matsushita T, Maruyama M. Rhof promotes murine marginal zone B cell development. Nagoya J Med Sci, 2014 Aug;76(3-4):293-305.
  4. Kihara R, Nagata Y, Kiyoi H, Kato T, Yamamoto E, Suzuki K, Chen F, Asou N, Ohtake S, Miyawaki S, Miyazaki Y, Sakura T, Ozawa Y, Usui N, Kanamori H, Kiguchi T, Imai K, Uike N, Kimura F, Kitamura K, Nakaseko C, Onizuka M, Takeshita A, Ishida F, Suzushima H, Kato Y, Miwa H, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Ogawa S, Naoe T. Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients. Leukemia, 2014 Aug;28(8):1586-95.
  5. Shimada K, Tomita A, Saito S, Kiyoi H. Effectiveness of ofatumumab to rituximab resistant CLL/SLL cells with reduced CD20 protein expression. Br J Haematol, 2014 Aug;166(3):455-7.
  6. Terakura S, Nishida T, Inamoto Y, Ohashi H, Naoe T, Murata M. Successful unrelated cord blood transplantation for adult acquired aplastic anemia using reduced intensity conditioning without ATG. Immunol Lett, 2014 Jul;160(1):99-101.
  7. Nishiwaki S, Nakayama T, Murata M, Nishida T, Terakura S, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Miyamura K, Ito M, Takeshita K, Kato H, Toyokuni S, Nagao K, Ueda R, Naoe T. Dexamethasone palmitate ameliorates macrophages-rich graft-versus-host disease by inhibiting macrophage functions. PLoS One, 2014 May; 9(5):e96252.
  8. Kato T, Nishida T, Ito Y, Murase M, Murata M, Naoe T. Correlations of programmed death 1 expression and serum IL-6 level with exhaustion of cytomegalovirus-specific T cells after allogeneic hematopoietic stem cell transplantation. Cell Immunol, 2014 Mar-Apr;288(1-2):53-59.
  9. Murata M, Nishida T, Taniguchi S, Ohashi K, Ogawa H, Fukuda T, Mori T, Kobayashi H, Nakaseko C, Yamagata N, Morishima Y, Nagamura-Inoue T, Sakamaki H, Atsuta Y, Suzuki R, Naoe T. Allogeneic transplantation for primary myelofibrosis with bone marrow, peripheral blood, or umbilical cord blood: An analysis of the JSHCT. Bone Marrow Transplant, 2014 Mar;49(3):355-60.
  10. Yasuda T, Ueno T, Fukumura K, Yamato A, Ando M, Yamaguchi H, Soda M, Kawazu M, Sai E, Yamashita Y, Murata M, Kiyoi H, Naoe T, Mano H. Leukemic evolution of donor-derived cells harboring IDH2 and DNMT3A mutations after allogeneic stem cell transplantation. Leukemia, 2014 Feb;28(2):426-8.
  11. Tokunaga T, Tomita A, Sugimoto K, Shimada K, Iriyama C, Hirose T, Shirahata-Adachi M, Suzuki Y, Mizuno H, Kiyoi H, Asano N, Nakamura S, Kinoshita T, Naoe T. De novo diffuse large B-cell lymphoma with a CD20 immunohistochemistry-positive and flow cytometry-negative phenotype: molecular mechanisms and correlation with rituximab sensitivity. Cancer Sci, 2014 Jan;105(1):35-43.

• 2013年

  1. Imahashi N, Nishida T, Ito Y, Kawada JI, Nakazawa Y, Toji S, Suzuki S, Terakura S, Kato T, Murata M, Naoe T. Identification of a novel HLA-A*24:02-restricted adenovirus serotype 11-specific CD8+ T-cell epitope for adoptive immunotherapy.\tMol Immunol, 2013 Dec;56(4):399-405.
  2. Hayakawa F, Sugimoto K, Harada Y, Hashimoto N, Ohi N, Kurahashi S, Naoe T.\t A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases. Blood Cancer J, 2013 Nov;3:e166.
  3. Murata M, Nakasone H, Kanda J, Nakane T, Furukawa T, Fukuda T, Mori T, Taniguchi S, Eto T, Ohashi K, Hino M, Inoue M, Ogawa H, Atsuta Y, Nagamura-Inoue T, Yabe H, Morishima Y, Sakamaki H, Suzuki R. Clinical factors predicting the response of acute graft-versus-host disease to corticosteroid therapy: an analysis from the GVHD working group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant, 2013 Aug;19(8):1183-9.
  4. Suzuki N, Kunishima S, Ikejiri M, Maruyama S, Sone M, Takagi A, Ikawa M, Okabe M, Kojima T, Saito H, Naoe T, Matsushita T. Establishment of Mouse Model of MYH9 Disorders: Heterozygous R702C Mutation Provokes Macrothrombocytopenia with Leukocyte Inclusion Bodies, Renal Glomerulosclerosis and Hearing Disability. PLoS One, 2013 Aug;8(8):e71187.
  5. Niimi K, Kiyoi H, Ishikawa Y, Hayakawa F, Kurahashi S, Kihara R, Tomita A, Naoe T. GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation. Leukemia Research Reports, 2013 Mar 19;2(1):21-5.
  6. Yasuda T, Suzuki R, Ishikawa Y, Terakura S, Inamoto Y, Yanada M, Nagai H, Ozawa Y, Ozeki K, Atsuta Y, Emi N, Naoe T. Randomized controlled trial comparing ciprofloxacin and cefepime in febrile neutropenic patients with hematological malignancies. Int J Infect Dis, 2013 Jun;17(6):e385-90.
  7. Tomita A, Kiyoi H, Naoe T. Mechanisms of action and resistance to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O 3) in acute promyelocytic leukemia. Int J Hematol\t, 2013 Jun;97(6):717-25.

• 2012年

  1. Mizuno H, Nakayama T, Miyata Y, Saito S, Nishiwaki S, Nakao N, Takeshita K, Naoe T. Mast cells promote the growth of Hodgkin's lymphoma cell tumor by modifying the tumor microenvironment that can be perturbed by bortezomib. Leukemia, 2012 Oct;26(10):2269-76.
  2. Minami Y, Abe A, Minami M, Kitamura K, Hiraga J, Mizuno S, Ymamoto K, Sawa M, Inagaki Y, Miyamura K, Naoe T. Retention of CD34+ CML stem/progenitor cells during imatinib treatment and rapid decline after treatment with second-generation BCR-ABL inhibitors. Leukemia, 2012 Sep;26(9):2142-3.
  3. Kuwatsuka Y, Kohno A, Terakura S, Saito S, Shimada K, Yasuda T, Inamoto Y, Miyamura K, Sawa M, Murata M, Karasuno T, Taniguchi S, Nagafuji K, Atsuta Y, Suzuki R, Fukumoto M, Naoe T, Morishita Y; Nagoya Blood and Marrow Transplantation Group. Phase II study of dose-modified busulfan by real-time targeting in allogeneic hematopoietic stem cell transplantation for myeloid malignancy.Cancer Sci, 2012 Sep;103(9):1688-94.
  4. Shimada K, Tomita A, Minami Y, Abe A, Hind CK, Kiyoi H, Cragg MS, Naoe T. CML cells expressing the TEL/MDS1/EVI1 fusion are resistant to imatinib-induced apoptosis through inhibition of BAD, but are resensitized with ABT-737. Exp Hematol, 2012 Sep;40(9):724-737.
  5. Nishiwaki S, Nakayama T, Saito S, Mizuno H, Ozaki T, Takahashi Y, Maruyama S, Nishida T, Murata M, Kojima S, Naoe T. Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis. Int J Hematol, 2012 Sep;96(3):295-300.
  6. Sugimoto T, Tomita A, Abe A, Iriyama C, Kiyoi H, Naoe T. Chimeric antisense RNA derived from chromosomal translocation modulates target gene expression. Haematologica, 2012 Aug;97(8):1278-80.
  7. Tomita A, Shirasugi Y, Ito T, Tsurumi H, Naoe T. Extravascular hemolytic attack after eculizumab therapy for paroxysmal nocturnal hemoglobinuria. Ann Hematol, 2012 Jul;91(7):1139-41.
  8. Watanabe K, Minami Y, Ozawa Y, Miyamura K, Naoe T. T315I mutation in Ph-positive acute lymphoblastic leukemia is associated with a highly aggressive disease phenotype: three case reports. Anticancer Res, 2012 May;32(5):1779-83.
  9. Kajiguchi T, Katsumi A, Tanizaki R, Kiyoi H, Naoe T. Y654 of β-catenin is essential for FLT3/ITD-related tyrosine phosphorylation and nuclear localization of β-catenin. Kajiguchi T, Katsumi A, Tanizaki R, Kiyoi H, Naoe T. Eur J Haematol, 2012 Apr;88(4):314-20.
  10. Nishiwaki S, Nakayama T, Murata M, Nishida T, Sugimoto K, Saito S, Kato T, Mizuno H, Imahashi N, Seto A, Ozawa Y, Goto T, Koyama D, Yokohata E, Kubota N, Kamoshita S, Miyamura K, Matsumoto K, Ito M, Naoe T. Dexamethasone palmitate successfully attenuates hemophagocytic syndrome after allogeneic stem cell transplantation: macrophage-targeted steroid therapy. Int J Hematol, 2012 Apr;95(4):428-33.
  11. Kato T, Terakura S, Murata M, Sugimoto K, Murase M, Iriyama C, Tomita A, Abe A, Suzuki M, Nishida T, Naoe T. Escape of leukemia blasts from HLA-specific CTL pressure in a recipient of HLA one locus-mismatched bone marrow transplantation. Cell Immunol, 2012 Mar-Apr;276(1-2):75-82.
  12. Iriyama C, Tomita A, Hoshino H, Adachi-Shirahata M, Furukawa-Hibi Y, Yamada K, Kiyoi H, Naoe T. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome. Biochem Biophys Res Commun, 2012 Mar 23;419(4):662-9.
  13. Tokunaga T, Shimada K, Yamamoto K, Chihara D, Ichihashi T, Oshima R, Tanimoto M, Iwasaki T, Isoda A, Sakai A, Kobayashi H, Kitamura K, Matsue K, Taniwaki M, Tamashima S, Saburi Y, Masunari T, Naoe T, Nakamura S, Kinoshita T. Retrospective analysis of prognostic factors for angioimmunoblastic T-cell lymphoma: a multicenter cooperative study in Japan. Blood, 2012 Mar 22;119(12):2837-43.
  14. Yasuda T, Hayakawa F, Kurahashi S, Sugimoto K, Minami Y, Tomita A, Naoe T. B cell receptor-ERK1/2 signal cancels PAX5-dependent repression of BLIMP1 through PAX5 phosphorylation: a mechanism of antigen-triggering plasma cell differentiation. J Immunol, 2012 Jun 15;188(12):6127-34.

• 2011年

  1. Murase M, Nishida T, Onizuka M, Inamoto Y, Sugimoto K, Imahashi N, Murata M, Miyamura K, Kodera Y, Inoko H, Naoe T. Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT. Bone Marrow Transplant, 2011 Nov;46(11):1444-9.
  2. Saito S, Nakayama T, Hashimoto N, Miyata Y, Egashira K, Nakao N, Nishiwaki S, Hasegawa M, Hasegawa Y, Naoe T. Mesenchymal stem cells stably transduced with a dominant-negative inhibitor of CCL2 greatly attenuate bleomycin-induced lung damage. Am J Pathol, 2011 Sep;179(3):1088-94.
  3. Goto E, Tomita A, Hayakawa F, Atsumi A, Kiyoi H, Naoe T. Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment. Blood. 2011 Aug 11;118(6):1600-9.
  4. Terakura S, Atsuta Y, Sawa M, Ohashi H, Kato T, Nishiwaki S, Imahashi N, Yasuda T, Murata M, Miyamura K, Suzuki R, Naoe T, Ito T, Morishita Y. A prospective dose-finding trial using a modified continual reassessment method for optimization of fludarabine plus melphalan conditioning for marrow transplantation from unrelated donors in patients with hematopoietic malignancies. Ann Oncol. 2011 Aug;22(8):1865-71.
  5. Ishikawa Y, Kiyoi H, Naoe T. Prevalence and clinical characteristics of N-terminally truncated WT1 expression in acute myeloid leukemia. Leukemia Res, 2011 May;35(5):685-8.
  6. Kurahashi S, Hayakawa F, Miyata Y, Yasuda T, Minami Y, Tsuzuki S, Abe A, Naoe T. PAX5-PML acts as a dual dominant-negative form of both PAX5 and PML. Oncogene, 2011 Apr 14;30(15):1822-30.
  7. Katsumi A, Kiyoi H, Abe A, Tanizaki R, Iwasaki T, Kobayashi M, Matsushita T, Senga T, Kohno T, Kojima T, Kaibuchi K, Hamaguchi M, Naoe T. FLT3/ITD regulates leukaemia cell adhesion through α4β1 integrin and Pyk2 signaling. Eur J Haematol, 2011 Mar;86(3):191-8.
  8. Sakai K, Ishikawa Y, Mori Y, Kobayashi M, Iriyama C, Ozawa Y, Suzuki T, Minami Y, Ishikawa K, Kaneda N, Naoe T, Kiyoi H. A novel insertion mutation of K294RGG within BCR-ABL kinase domain confers imatinib-resistance: sequential analysis of the clonal evolution in a patient with chronic myeloid leukemia in blast crisis. Int J Hematol, 2011 Feb;93(2):237-42.

• 2010年

  1. Tsujimura A, Kiyoi H, Shiotsu Y, Ishikawa Y, Mori Y, Ishida H, Toki T, Ito E, Naoe T. Selective KIT inhibitor KI-328 and HSP90 inhibitor show different potency against the type of KIT mutations recurrently identified in acute myeloid leukemia. Int J Hematol, 2010 Nov;92(4):624-33.
  2. Minami Y, Kajiguchi T, Abe A, Ohno T, Kiyoi H, Naoe T. Expanded distribution of the T315I mutation among hematopoietic stem cells and progenitors in a chronic myeloid leukemia patient during imatinib treatment. Int J Hematol, 2010 Nov;92(4):664-6.
  3. Ishikawa Y, Kiyoi H, Watanabe K, Miyamura K, Nakano Y, Kitamura K, Kohno A, Sugiura I, Yokozawa T, Hanamura A, Yamamoto K, Iida H, Emi N, Suzuki R, Ohnishi K, Naoe T. Trough plasma concentration of imatinib reflects BCR-ABL kinase inhibitory activity and clinical response in chronic-phase chronic myeloid leukemia: a report from the BINGO study. Cancer Sci, 2010 Oct;101(10):2186-92.
  4. Nakao N, Nakayama T, Yahata T, Muguruma Y, Saito S, Miyata Y, Yamamoto K, Naoe T. Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo: advantages over bone marrow-derived mesenchymal stem cells. Am J Pathol, 2010 Aug;177(2):547-54.
  5. Suzuki M, Abe A, Imagama S, Nomura Y, Tanizaki R, Minami Y, Hayakawa F, Ito Y, Katsumi A, Yamamoto K, Emi N, Kiyoi H, Naoe T. BCR-ABL-independent and RAS / MAPK pathway-dependent form of imatinib resistance in Ph-positive acute lymphoblastic leukemia cell line with activation of EphB4. Eur J Haematol, 2010 Mar;84(3):229-38.
  6. Tanizaki R, Nomura Y, Miyata Y, Minami Y, Abe A, Hanamura A, Sawa M, Murata M, Kiyoi H, Matsushita T, Naoe T. Irrespective of CD34 expression, lineage-committed cell fraction reconstitutes and re-establishes transformed Philadelphia chromosome-positive leukemia in NOD/SCID/IL-2Rgammac-/- mice. Cancer Sci, 2010 Mar;101(3):631-8.
  7. Inamoto Y, Murata M, Katsumi A, Kuwatsuka Y, Tsujimura A, Ishikawa Y, Sugimoto K, Onizuka M, Terakura S, Nishida T, Kanie T, Taji H, Iida H, Suzuki R, Abe A, Kiyoi H, Matsushita T, Miyamura K, Kodera Y, Naoe T. Donor single nucleotide polymorphism in the CCR9 gene affects the incidence of skin GVHD. Bone Marrow Transplant, 2010 Feb;45(2):363-9.
  8. Shimada K, Murase T, Matsue K, Okamoto M, Ichikawa N, Tsukamoto N, Niitsu N, Miwa H, Asaoku H, Kosugi H, Kikuchi A, Matsumoto M, Saburi Y, Masaki Y, Yamamoto K, Yamaguchi M, Nakamura S, Naoe T, Kinoshita T; IVL Study Group in Japan. Central nervous system involvement in intravascular large B-cell lymphoma: a retrospective analysis of 109 patients. Cancer Sci, 2010 Jun;101(6):1480-6.

研究キーワード

白血病、悪性リンパ腫、多発性骨髄腫、骨髄異形成症候群、再生不良性貧血、溶血性貧血、特発性血小板減少性紫斑病、血友病、von Willebrand病、遺伝子変異、染色体異常、分子標的薬、キナーゼ阻害剤、抗体治療薬、免疫療法、移植免疫、分化誘導療法、エピジェネティクス

血液・腫瘍内科学講座　独自ホームページへ

血液・腫瘍内科学　オープンキャンパス

大学院修士・博士課程学生募集

血液・腫瘍内科学教室では、血液疾患における分子病態の解明を進め、新しい診断・治療技術の開発とEBMを作りうる質の高い臨床研究を推進することを目指しています。「最終的に患者さんに還元されうるオリジナリティーあふれる研究成果」を世界に発信させようと、多くの大学院生が日夜頑張っています。各プロジェクトは、研究能力の高いプロジェクトリーダー（PI）のもとに遂行され、研究の実施から論文発表まで一貫した指導が受けられる体制が維持されています。当教室では、これらの研究を推進していただける大学院生を広く募集しています。血液・腫瘍内科学での修士課程、博士課程の研究に興味をお持ちの方は、是非当科窓口へご連絡下さい。実際のプログラム見学も随時受け付けております。