2012 Fiscal Year Final Research Report
The new development of treatment for graft-versus-host disease through memory T cells
Project/Area Number |
22591063
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Kyushu University |
Principal Investigator |
KATO Koji 九州大学, 大学病院・血液腫瘍内科, 助教 (20571764)
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Project Period (FY) |
2010 – 2012
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Keywords | 造血幹細胞移植学 |
Research Abstract |
Histone methylation is thought to be important for regulating antigen-driven T cell responses. However,little is known about the impact of modulating histone methylation on inflammatory T cell responses.We demonstrate that in vivo administration of the histone methylation inhibitor 3-deazaneplanocin A (DZNep) arrests ongoing graft-versus-host disease(GVHD)in mice after alloge neic bone marrow transplantation (BMT).DZNep caused selective apoptosis in alloantigen-activated T cells mediating host tissue injury.This effect was associated with DZNep's ability to selectively reduce trimethylation of histone H3 lysine 27 (H3K27me3), deplete the histone methyltransferase Ezh2 specific to H3K27me3 and activate pro-apoptotic gene Bim repressed by Ezh2 in antigenic-activated T cells. In contrast, DZNep did not impact the survival of alloantigen-unresponsive T cells in vivo and naive T cells stimulated by IL-2 or IL-7 in vitro. Importantly, inhibition of histone methylation by DZNep treatment in vivo preserved the anti-leukemia activity of donor T cells and did not impair the recovery of hematopoiesis and lymphocytes, leading to significantly improved survival of recipients after allogeneic BMT.Our findings indicate that modulation of histone methylation may have significant implications in the development of novel approaches to treat ongoing GVHD and other T cell-mediated inflammatory disorders in a broad context.
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Research Products
(29 results)
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[Journal Article] Diffuse panbronchiolitis after humanized anti-CCR4 monoclonal antibody therapy for relapsed adult T-cell leukemia/lymphoma.2013
Author(s)
Kato K, Miyamoto T, Numata A, Nakaike T, Oka H, Yurino A, Kuriyama T, Mori Y, Yamasaki S, Muta T, Takenaka K, Iwasaki H, Teshima T, Akashi K.
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Journal Title
Int J Hematol.
Volume: 97
Pages: 430-2
DOI
Peer Reviewed
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[Journal Article] nhibition of histone methylation arrests ongoing graft-versus-host disease in mice by selectively inducing apoptosis of alloreactive effector T cells.2012
Author(s)
He S*, Wang J*, Kato K*, Xie F, Varambally S, Mineishi S, Kuick R, Mochizuki K, Liu Y, Nieves E, Mani RS, Chinnaiyan AM, Marquez VE, Zhang Y (*Equal contribution to this work)
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Journal Title
IBlood.
Volume: 119
Pages: 1274-82
DOI
Peer Reviewed
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[Journal Article] Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: a nationwide retrospective study.2012
Author(s)
Ishida T, Hishizawa M, Kato K, Tanosaki R, Fukuda T, Taniguchi S, Eto T, Takatsuka Y, Miyazaki Y, Moriuchi Y, Hidaka M, Akashi K, Uike N, Sakamaki H, Morishima Y, Kato K, Suzuki R, Nishiyama T, Utsunomiya A.
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Journal Title
Blood.
Volume: 120
Pages: 1734-41
DOI
Peer Reviewed
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[Journal Article] Initial low-dose valganciclovir as a preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients.2012
Author(s)
Takenaka K, Nagafuji K, Takase K, Kamimura T, Mori Y, Ito Y, Nishi Y, Henzan H, Kato K, Harada N, Eto T, Miyamoto T, Teshima T, Akashi K.
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Journal Title
Int J Hematol
Volume: 96
Pages: 94-100
DOI
Peer Reviewed
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[Journal Article] Different risk factors related to adenovirus- or BK virus-associated hemorrhagic cystitis following allogeneic stem cell transplantation.2012
Author(s)
Mori Y, Miyamoto T, Kato K, Kamezaki K, Kuriyama T, Oku S, Takenaka K, Iwasaki H, Harada N, Shiratsuchi M, Abe Y, Nagafuji K, Teshima T, Akashi K.
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Journal Title
Biol Blood Marrow Transplant.
Volume: 18
Pages: 458-65
DOI
Peer Reviewed
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[Journal Article] Low incidence of adenovirus hemorrhagic cystitis following autologous hematopoietic stem cell transplantation in the rituximab era.2012
Author(s)
Mori Y, Miyamoto T, Kamezaki K, Kato K, Kikushige Y, Takashima S, Urata S, Shimoda S, Shimono N, Takenaka K, Iwasaki H, Nagafuji K, Teshima T, Akashi K.
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Journal Title
Am J Hematol.
Volume: 87
Pages: 828-30
DOI
Peer Reviewed
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[Journal Article] Notch signaling is a critical regulator of allogeneic CD4+ T cell responses mediating graft-versus-host disease.2011
Author(s)
Zhang Y, Sandy AR, Wang J, Radojcic V, Shan GT, Tran IT, Friedman A, Kato K, He S, Cui S, Hexner E, Frank DM, Emerson SG, Pear WS, Maillard I.
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Journal Title
Blood.
Volume: 117
Pages: 299-308
DOI
Peer Reviewed
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[Journal Article] for the Fukuoka Blood and Marrow Transplantation Group. ,Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group.2010
Author(s)
Numata A, Miyamoto T, Ohno Y, Kamimura T, Kamezaki K, Tanimoto T, Takase K, Henzan H, Kato K, Takenaka K, Fukuda T, Harada N, Nagafuji K, Teshima T, Akashi K, Harada M and Eto T
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Journal Title
Bone Marrow Transplant.
Volume: 45
Pages: 311-6
DOI
Peer Reviewed
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[Journal Article] High incidence of HHV6-associated encephalitis/myelitis following a second unrelated cord blood transplantation.2010
Author(s)
Mori Y, Miyamoto T, Nagafuji K, Kamezaki K, Yamamoto A, Saito N, Kato K, Takenaka K, Iwasaki H, Harada N, Abe Y, Teshima T, Akashi K.
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Journal Title
Biol Blood Marrow Transplant.
Volume: 16
Pages: 1596-1602
DOI
Peer Reviewed
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