Internal Medicine

Hematology

  • Professor: Takanori Teshima
  • Lecturer: Takeshi Kondo
  • Assistant Professor: Masahiro Onozawa*
  • Assistant Professor: Masao Nakagawa
  • Phone: +81-11-706-7214
  • FAX: +81-11-706-7823
  • *concurrent
Hematopoietic disorders cause various hematological diseases such as leukemias, myelodysplastic sydromes, lymphomas, myelomas, anemias, hemorrhagic tendency, and coagulopathy. We treat patients with hematological diseases, using the most effective therapy at present. Moreover, we try to define the pathophysiological findings of various hematological diseases from the point of biological, cytogenetical, molecular, and immunological views.

Research

Our main research aim is to clarify the immunopathogenicity of graft-versus-host disease (GVHD) and to induce graft-versus-leukemia/tumor (GVL/GVT) effect after allogeneic hematopoietic stem cell transplantation (HSCT). In human, we found that inhibitory NK cell receptor-positive T cells took an important role in regulating GVHD, preserving GVL/GVT effect. In clinical settings, the percentage of hematological diseases in one year is as follows: non-Hodgkin lymphomas, 40%; acute leukemias, 16%; myeloproliferative diseases, 9%; multiple myelomas, 8%; myelodysplastic syndromes, 5%; idiopathic thrombocytopenic purpura, 2%; Hodgkin lymphomas, 2%, aplastic anemia, 1%; others, 17%. For the patients with hematological malignancies, we treat them with chemotherapeutic agents and/or monoclonal antibodies, and with molecular targeting agents. In the case of patients who can be treated with hematopoietic stem cell transplantation, such a procedure is routinely performed. The average numbers of autologous HSCT and allogeneic HSCT in one year is about 15 and 40 cases, respectively. Sources of allogeneic HSCT are comprised of bone marrow stem cells, peripheral blood stem cells, and cord blood stem cells. Conditioning regimens include myeloablative and non-myeloablative procedures. By our own conditioning regimen of allogeneic HSCT, an excellent outcome for acute lymphoblastic leukemia is obtained (3-year survival: 90%). Other research themes are to analyze leukemogenesis, innate immunity against infectious pathogens and cancer cells, stem cell characteristics, and so on.

Education

We take part in the courses of Oncology (standard therapies and molecular targeting therapies against hematological malignancies) and Hematology (hematopoiesis, hematopoietic system, leukemias, lymphomas, anemias, myelodysplastic syndromes, myeloproliferative diseases, hematopoietic stem cell transplantation, hemorrhagic tendency and coagulopathy, infection control, and transfusion medicine) for the third and fourth grades undergraduate students. Moreover, we take part in clinical practice for the fifth and sixth grades undergraduate students. For the graduate students who take master or doctoral course, several classes regarding hematological researches are open. Almost all the classes are given in Japanese.

International Activities

Recent invited talks in international conference
1. Imamura M (2011) The Second Meeting of Asian Cellular Therapy Organization, Miyazaki.
2. Imamura M (2006) 11th Annual Summer Meeting of the Korean Society of Hematopoietic Stem Cell Transplantation, Seoul.
Fig1
Fig2
1 Medium-dose VP/CY/TBI conditioning regimen
2 Cumulative incidence of relapse, transplant-related mortality, and overall survival

Selected Publications

1. Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F, Goto S, Kameoka S, Fujikura D, Yamada T, Mizutani T, Kazumata M, Sato M, Tanaka J, Asaka M, Ohba Y, Miyazaki T, Imamura M, Takaoka A (2011) ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I for antiviral responses. Nat. Immunol. 12: 37-44.
2. Shono Y, Ueha S, Wang Y, Abe J, Kurachi M, Matsuno Y, Sugiyama T, Nagasawa T, Imamura M, Matsushima K (2010) Bone marrow graft-versus-host disease: early destruction of hematopoietic niche following MHC-mismatched hematopoietic stem cell transplantation. Blood 115: 5401-5411.
3. Shiratori S, Yasumoto A, Tanaka J, Shigematsu A, Yamamoto S, Nishio M, Hashino S, Morita R, Takahata M, Onozawa M, Kahata K, Kondo T, Ota S, Wakasa K, Sugita J, Koike T, Asaka M, Imamura M (2008) A retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia/lymphoma (ATL): clinical impact of graft-versus-leukemia/lymphoma effect. Biol. Blood Marrow Transplant. 14: 817-823.
4. Shigematsu A, Kondo T, Yamamoto S, Sugita J, Onozawa M, Kahata K, Endo T, Shiratori S, Ota S, Obara M, Wakasa K, Takahata M, Takeda Y, Tanaka J, Hashino S, Nishio M, Koike T, Asaka M, Imamura M (2008) Excellent outcome of allogeneic hematopoietic stem cell transplantation using a conditioning regimen with medium-dose VP-16, cyclophosphamide and total body irradiation for adult patients with acute lymphoblastic leukemia. Biol. Blood Marrow Trasnplant. 14: 568-575.
5. Tanaka J, Iwao N, Toubai T, Tsutsumi Y, Miura Y, Kato N, Shigematsu A, Yamane M, Ota S, Kondo T, Kobayashi T, Takeda H, Kobayashi M, Asaka M, Imamura M (2005) Cytolytic activity against primary leukemic cells by inhibitory NK cell receptor (CD94/NKG2A)-expressing T cells expanded from various sources of blood mononuclear cells. Leukemia 19: 486-489.
6. Kato N, Tanaka J, Sugita J, Toubai T, Miura Y, Ibata M, Shono Y, Ota S, Kondo T, Asaka M, Imamura M (2007) Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Leukemia 35: 2103-2108.
7. Tanaka J, Toubai T, Tsutsumi Y, Miura Y, Kato N, Umehara S, Kahata K, Mori A, Toyoshima N, Ota S, Kobayashi T, Kobayashi M, Kasai M, Asaka M, Imamura M (2004) Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Blood 104: 768-774.