Hematology / Oncology

1976,

M.D., Nagoya University School of Medicine

1976-1980,

Resident, Internal Medicine, Nagoya 1st Red Cross Hospital

1981-1989,

Clinical Fellow, Nagoya University Hospital

1989-1995,

Assistant Professor/Associate Professor, Nagoya University Branch Hospital

1996-2001,

Associate Professor, Nagoya University Hospital

2001-,

Professor, Nagoya University Graduate School of Medicine

Development of target therapy for hematological malignancies

Based on the molecular difference between cancer and normal tissues, molecule-targeted therapy has been developed for malignancies by targeting a specific molecule. Imatinib against Abl kinase and rituximab against CD20 are typical examples for leukemia and lymphoma, respectively, and have significantly improved treatment outcome. However, the benefits are given to limited number of patients. Furthermore, the resistance to the targeted therapy is emerging as a clinical problem. Our research are focused on the molecular understanding of the pathogenesis in hematological malignancies, developing molecular diagnosis and new treatments, and overcome of the resistance.

1. We have found the clinical prevalence and significance of FLT3 mutations in acute myeloid leukemia (AML). We also investigated abnormal signaling and developed FLT3 kinase inhibitors and started the phase I trial.

2. We have conducted JALSG, Japan Adults Leukemia Study Group, to establish standard therapy for leukemia and to develop clinical research for refractory leukemia.

3. We have developed the mice model of human leukemia using NOG immunodeficiency mice and identified leukemia niche as well as leukemia stem cells.

4. We have studied the mechanism of GVHD, an immune response of graft against host after hematopoietic stem cell transplantation, and identified allergenic antigens.

5. We conduct new clinical research for leukemia in which therapies are stratified by the molecular diagnosis.

6. We develop new targeted therapy to overcome the resistance to current therapies.

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1. Minami Y et al. Transformation of E2A-Deficient Pluripotent Progenitors by BCR-ABL Generates Leukemic Stem Cells in the GMP Compartment. Proc. Nat.l Acad. Sci. USA. in press (2008)
2. Hayakawa F et al. Acetylation of PML is involved in histone deacetylase Inhibitor-mediated apoptosis. J. Biol. Chem. in press (2008)
3. Shimada K et al. Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan. J. Clin. Oncol. 26: 3189-3195 (2008)
4. Kiyoi H et al. A novel FLT3 inhibitor FI-700 selectively suppresses the growth of leukemia cells with FLT3 mutations. Clin. Cancer Res. 13: 4575-4582 (2007)
5. Yoshida H et al. PML-retinoic acid receptor alpha inhibits PML IV enhancement of PU.1-induced C/EBPepsilon expression in myeloid differentiation. Mol. Cell Biol. 27: 5819-5834 (2007)
6. Ninomiya M et al. Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice. Leukemia 21: 136-142 (2007)
7. Yanada M et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J. Clin. Oncol. 24: 460-466 (2006)
8. Suzuki T et al. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood 106: 2854-2861 (2005)
9. Katsumi A et al. Integrin activation and matrix binding mediate cellular responses to mechanical stretch. J. Biol. Chem. 280: 16546-16549 (2005)
10. Ozeki K et al. Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood 103: 1901-1908 (2004)
11. Minami Y et al. Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia. Blood 102: 2969-2975 (2003)
12. Akatsuka Y et al. Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens. J. Exp. Med. 197: 1489-500 (2003)
13. Kiyoi H et al. Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene 21: 2555-2263 (2002)
14. Yamamoto Y et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood 97: 2434-2439 (2001)
15. Hayakawa F et al. Tandem-duplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3-dependent cell lines. Oncogene 19: 624-631 (2000)
16. Naoe T et al. Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia. Clin. Cancer Res. 6: 4091-4095 (2000)

1992 Encouraging prize from Japan Society of Hematology
2004 Research award from Japan Leukaemia Research Fund