Clinocopathological analysis of HTLV-I associated genes of HBZ and tax in the tumor genesis of ATLL

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390104
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kurume University
• Principal Investigator: KOICHI Ohshima Kurume University, 医学部, 教授 (50203766)
• Co-Investigator(Kenkyū-buntansha): SUGITA Yasuo 久留米大学, 医学部, 教授 (80216316)
• Project Period (FY): 2008 – 2010
• Keywords: ウイルス / 病理学 / ATLL / HTLV-I / 腫瘍

Research Abstract

Adult T-cell leukemia/lymphoma (ATLL) is a T-cell malignancy associated with human T-cell leukemia virus type 1 (HTLV-1). The HTLV-1 provirus genome has the pX region which encodes tax and HTLV-1 basic leucine zipper factor (HBZ). The previous studies have reported that the tax gene is expressed in few ATLL cases, but the HBZ gene in all ATLL cases. In this study, HBZ-expression was demonstrated in all cases of ATLL cell line and ATLL model mouse, and human ATLL cases. However, Tax expression was rare. In addition,we analyzed the expression of FOXP3, a key molecule of regulatory T cells. The expression was detected in about one third of ATLL. And FOXP3 expression is associated with an immunosuppressive state.

Research Products

• [Journal Article] Regression of rectal mucosa-associated lymphoid tissue (MALT) lymphoma after antibiotic treatments. (2010)
  • Author(s): Niino D, Yamamoto K, Tsuruta O, Maeda T, Yakushijin Y, Aoki R, Kimura Y, Hashikawa K, Kiyasu J, Takeuchi M, Sugita Y, Ohshima K
  • Journal Title: Pathol Int. 60(6) Pages: 438-42
• [Journal Article] Ratio of M2 macrophage expression is closely associated with poor prognosis for Angioimmunoblastic T-cell lymphoma (AITL) (2010)
  • Author(s): Niino D, Komohara Y, Murayama T, Aoki R, Kimura Y, Hashikawa K, Kiyasu J, Takeuchi M, Suefuji N, Sugita Y, Takeya M, Ohshima K
  • Journal Title: Pathol Int. 60(4) Pages: 278-83
• [Journal Article] Ueda RPhase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody (2010)
  • Author(s): Yamamoto K, Utsunomiya A, Tobinai K, Tsukasaki K, Uike N, Uozumi K, Yamaguchi K, Yamada Y, Hanada S, Tamura K,Nakamura S, Inagaki H, Ohshima K, Kiyoi H, Ishida T, Matsushima K, Akinaga S, Ogura M, Tomonaga M
  • Journal Title: in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma J Clin Oncol. 20;28(9) Pages: 1591-8
• [Journal Article] Linkage of expression of chemokine receptors (CXCR3 and CCR4) and cytotoxic molecules in Peripheral T cell lymphoma, not otherwise specified and ALK-negative anaplastic large cell Lymphoma. (2010)
  • Author(s): Asano N, Suzuki R, Ohshima K, Kagami Y, Ishida F, Yoshino T, Ogawa H,Morishima Y, Nakamura S
  • Journal Title: Int J Hematol. 91(3) Pages: 26-35
• [Journal Article] Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma. (2010)
  • Author(s): Sato H, Oka T, Shinnou Y, Kondo T, Washio K, Takano M, Takata K, Morito T, Huang X, Tamura M, Kitamura Y, Ohara N, Ouchida M, Ohshima K, Shimizu K, Tanimoto M, Takahashi K, Matsuoka M, Utsunomiya A, Yoshino T
  • Journal Title: Am J Pathol. 176(1) Pages: 402-15
• [Journal Article] Prognostic significance of S-phase kinase-associated protein 2 and p27kip1 in patients with diffuse large B-cell lymphoma : effects of rituximab. (2009)
  • Author(s): Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Shimoda K, Okamura T
  • Journal Title: Ann Oncol. 4(Epub ahead of print)
• [Journal Article] Phenotype for activated tissue macrophages in histiocytic necrotizing lymphadenitis. (2009)
  • Author(s): Nomura Y, Takeuchi M, Yoshida S, Sugita Y, Niino D, Kimura Y, Shimizu K, Aoki R, Suefuji N, Hirose S, Kikuchi M, Ohshima K.
  • Journal Title: Pathol Int. 59(9) Pages: 631-5
• [Journal Article] Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. (2009)
  • Author(s): Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Ogawa R, Shimoda K, Yamashita K, Suzuki K, Suzushima H, Tsukazaki K, Higuchi M, Utsunomiya A, Iwahashi M, Imamura Y, Tamura K, Suzumiya J, Yoshida M, Abe Y, Matsumoto T, Okamura T
  • Journal Title: Cancer Sci. 100(10) Pages: 1842-7
• [Journal Article] Phase I/II Study of Concurrent Chemoradiotherapy for Localized Nasal Natural Killer/T-Cell Lymphoma : Japan Clinical Oncology Group Study JCOG0211. (2009)
  • Author(s): Yamaguchi M, Tobinai K, Oguchi M, Ishizuka N, Kobayashi Y, Isobe Y, Ishizawa K, Maseki N, Itoh K, Usui N, Wasada I, Kinoshita T, Ohshima K, Matsuno Y, Terauchi T, Nawano S, Ishikura S, Kagami Y, Hotta T, Oshimi K
  • Journal Title: J Clin Oncol. 5(Epub ahead of print)
• [Journal Article] Hepatocellular apoptosis associated with cytotoxic T/natural killer-cell infiltration in chronic active EBV infection. (2009)
  • Author(s): Nomura Y, Kimura H, Karube K, Yoshida S, Sugita Y, Niino D, Shimizu K, Kimura Y, Aoki R, Kiyasu J, Takeuchi M, Hashikawa K, Hirose S, Ohshima K
  • Journal Title: Pathol Int. 59(7) Pages: 438-42
• [Journal Article] Clinical significance of co-expression of CD21 and LFA-1 in B-cell lymphoma. (2009)
  • Author(s): Tanimoto K, Yakushijin Y, Fujiwara H, Otsuka M, Ohshima K, Sugita A, Sakai A, Hato T, Hasegawa H, Yasukawa M
  • Journal Title: Int J Hematol. 89(4) Pages: 497-507
• [Journal Article] Oncogene associated cDNA microarray analysis shows PRAME gene expression is a marker for response to anthracycline containing chemotherapy in patients with diffuse large B-cell lymphoma. (2009)
  • Author(s): Kawano R, Karube K, Kikuchi M, Takeshita M, Tamura K, Uike N, Eto T, Ohshima K, Suzumiya J
  • Journal Title: J Clin Exp Hematop. 49(1) Pages: 1-7
• [Journal Article] Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV-1-infected T cells through enhanced NF-kappaB activity. (2009)
  • Author(s): Tomita M, Toyota M, Ishikawa C, Nakazato T, Okudaira T, Matsuda T, Uchihara JN, Taira N, Ohshiro K, Senba M, Tanaka Y, Ohshima K, Saya H, Tokino T, Mori N
  • Journal Title: Int J Cancer. 1;124(11) Pages: 2607-15
• [Journal Article] Expression of CXCL12 on pseudopalisading cells and proliferating microvessels in glioblastomas : an accelerated growth factor in glioblastomas. (2009)
  • Author(s): Komatani H, Sugita Y, Arakawa F, Ohshima K, Shigemori M
  • Journal Title: Int J Oncol. 34(3) Pages: 665-72
• [Journal Article] Correlation of decreased survival and IL-18 in bone metastasis. (2009)
  • Author(s): Okamoto M, Azuma K, Hoshino T, Imaoka H, Ikeda J, Kinoshita T, Takamori S, Ohshima K, Edakuni N, Kato S, Iwanaga T, Aizawa H
  • Journal Title: Intern Med. 48(10) Pages: 763-73
• [Journal Article] for the International Peripheral T-cell Lymphoma Project. The International Prognostic Index predicts outcome in aggressive adult T-cell leukemia/lymphoma : analysis of 126 patients from the International Peripheral T-cell Lymphoma Project. (2009)
  • Author(s): Suzumiya J, Ohshima K, Tamura K, Karube K, Uike N, Tobinai K, Gascoyne RD, Vose JM, Armitage JO, Weisenburger DD
  • Journal Title: Ann Oncol. 20 Pages: 715-721
• [Journal Article] rray comparative genomic hybridization analysis of PTCL-U reveals a distinct subgroup with genetic alterations similar to lymphoma-type adult T-cell leukemia/lymphoma. (2009)
  • Author(s): Nakagawa M, Nakagawa-Oshiro A, Karnan S, Tagawa H, Utsunomiya A, Nakamura S, Takeuchi I, Ohshima K, Seto M
  • Journal Title: Clin Cancer Res. 1;15(1) Pages: 30-8
• [Journal Article] IL-21 is expressed in Hodgkin lymphoma and activates STAT5 : evidence that activated STAT5 is required for Hodgkin lymphomagenesis. (2008)
  • Author(s): Scheeren FA, Diehl SA, Smit LA, Beaumont T, Naspetti M, Bende RJ, Blom B, Karube K, Ohshima K, van Noesel CJ, Spits H
  • Journal Title: Blood. 1;111(9) Pages: 4706-15
• [Journal Article] Histological characteristics of 21 Papua New Guinean children with high-grade B-cell lymphoma, which is frequently associated with EBV infection. (2008)
  • Author(s): Nomura Y, Lavu EK, Muta K, Niino D, Takeshita M, Hirose S, Nakamura S, Yoshino T, Kikuchi M, Ohshima K
  • Journal Title: Pathol Int. 58(11) Pages: 695-700
• [Journal Article] Characterization of de novo diffuse large B-cell lymphoma with a translocation of c-myc and immunoglobulin genes. (2008)
  • Author(s): Kikuchi A, Nakamura N, Kuze T, Sasaki Y, Abe M, Ohno H, Akasaka T, Nakamura S, Ohshima K, Ando K
  • Journal Title: Leuk Res. 32(8) Pages: 1176-82
• [Journal Article] Downregulation of RCAS1 and upregulation of cytotoxic T cells affects synovial proliferation and apoptosis in rheumatoid arthritis. (2008)
  • Author(s): Yoshida S, Higuchi F, Ishibashi Y, Goto M, Sugita Y, Nomura Y, Karube K, Shimizu K, Aoki R, Komatani H, Hashikawa K, Kimura Y, Nakashima M, Nagata K, Ohshima K
  • Journal Title: J Rheumatol. 35(9) Pages: 1716-22
• [Journal Article] Estimation of the relationship between caspase-3 expression and clinical outcome of Burkitt's and Burkitt-like lymphoma. (2008)
  • Author(s): Nomura Y, Yoshida S, Karube K, Takeshita M, Hirose S, Nakamura S, Yoshino T, Kikuchi M, Ohshima K
  • Journal Title: Cancer Sci. 99(8) Pages: 1564-9
• [Journal Article] BCL6 gene amplification/3q27 gain is associated with unique clinicopathological characteristics among follicular lymphoma without BCL2 gene translocation. (2008)
  • Author(s): Karube K, Ying G, Tagawa H, Niino D, Aoki R, Kimura Y, Hashikawa K, Suefuji N, Sugita Y, Nomura Y, Shimizu K, Yoshida S, Seto M, Ohshima K
  • Journal Title: Mod Pathol. 21(8) Pages: 973-8
• [Journal Article] De novo CD5+ diffuse large B-cell lymphoma : results of a detailed clinicopathological review in 120 patients. (2008)
  • Author(s): Yamaguchi M, Nakamura N, Suzuki R, Kagami Y, Okamoto M, Ichinohasama R, Yoshino T, Suzumiya J, Murase T, Miura I, Ohshima K, Nishikori M, Tamaru J, Taniwaki M, Hirano M, Morishima Y, Ueda R, Shiku H, Nakamura S
  • Journal Title: Haematologica. 93(8) Pages: 1195-202
• [Journal Article] Lymphoma Committee of Japanese Childhood Cancer and Leukemia.Favourable outcomes in children with diffuse large B-cell lymphoma treated by a short-term ALL-like regimen : a report on the NHL960 study from the Japanese Childhood Cancer and Leukemia Study Group. (2008)
  • Author(s): Tsurusawa M, Taga T, Horikoshi Y, Ogawa A, Kikuta A, Kanegane H, Matsushita T, Hyakuna N, Shimomura Y, Ohshima K
  • Journal Title: Leuk Lymphoma. 49(4) Pages: 734-9
• [Journal Article] High-grade mature B-cell lymphoma with Burkitt-like morphology : results of a clinicopathological study of 72 Japanese patients. (2008)
  • Author(s): Nomura Y, Karube K, Suzuki R, Ying G, Takeshita M, Hirose S, Nakamura S, Yoshino T, Kikuchi M, Ohshima K
  • Journal Title: Cancer Sci. 99(2) Pages: 246-52
• [Journal Article] CAEBV Study Group. Review : Proposed categorization of pathological states of EBV-associated T/natural killer-cell lymphoproliferative disorder (LPD) in children and young adults : overlap with chronic active EBV infection and infantile fulminant EBV T-LPD. (2008)
  • Author(s): Ohshima K, Kimura H, Yoshino T, Kim CW, Ko YH, Lee SS, Peh SC, Chan JK
  • Journal Title: Pathol Int. 58(4) Pages: 209-17
• [Journal Article] Estimation of apoptosis and cell proliferation in histiocytic necrotizing lymphadenitis using immunohistochemical double staining. (2008)
  • Author(s): Nomura Y, Sugita Y, Yoshida S, Karube K, Shimizu K, Aoki R, Hirose S, Kikuchi M, Ohshima K
  • Journal Title: Pathol Int. 58(2) Pages: 98-103
• [Journal Article] The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma. (2008)
  • Author(s): Karube K, Aoki R, Sugita Y, Yoshida S, Nomura Y, Shimizu K, Kimura Y, Hashikawa K, Takeshita M, Suzumiya J, Utsunomiya A, Kikuchi M, Ohshima K
  • Journal Title: Mod Pathol. 21(5) Pages: 617-25
• [Journal Article] Usefulness of flow cytometry for differential diagnosis of precursor and peripheral T-cell and NK-cell lymphomas : Analysis of 490 cases. (2008)
  • Author(s): Karube K, Aoki R, Nomura Y, Yamamoto K, Yoshida S, Shimizu K, Komatani H, Sugita Y, Ohshima K.
  • Journal Title: Pathol Int. 58(2) Pages: 89-97