p57KIP2 methylation as a prognostic biomarker of malignant lymphoma

• Project/Area Number: 22591055
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hematology
• Research Institution: National Hospital Organization Nagoya Medical Center
• Principal Investigator: NAGAI Hirokazu 独立行政法人国立病院機構(名古屋医療センター臨床研究センター), 臨床研究センター, 部長 (30360811)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 癌 / 悪性リンパ腫 / 予後予測因子 / がん抑制遺伝子 / p57KI2遺伝子 / 予後因子 / p57KIP2 / p57KIP2遺伝子

Research Abstract

Biomarkers are critical in the diagnosis and monitoring of diseases. This research was conducted to establish the molecular biomarker for malignant lymphoma. p57KIP2 gene was highly methylated in malignant lymphoma. This methylation was detected in lesions but also in peripheral blood serum DNAs of lymphoma patients. It would be an efficient and convenient marker for lymphoma.

Research Products

• [Journal Article] Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups. (2013)
  • Author(s): Kihara R, Watanabe T, Yano T, Uike N, Okamura S, Kawano F, Hanada S, Sunami K, Inoue N, Sawamura M, Yoshida S, Shimomura T, Kitano K, Kojima Y, Horibe K, Nagai H
  • Journal Title: Int J Hematol. Volume: 98(1) Pages: 98-102
• [Journal Article] Non-AIDS-defining hematological malignancies in HIV-infected patients : an epidemiological study in Japan. (2013)
  • Author(s): Hagiwara S, Yotsumoto M, Odawara T, AjisawaA, Uehira T, Nagai H, Tanuma J, and Okada S
  • Journal Title: AIDS. Volume: 27(2) Pages: 279-283
• [Journal Article] Prognosis of mature T cell lymphoma is poorer than that of diffuse large B cell lymphoma in IPI low-risk group, but not in intermediate- and high-risk groups. (2013)
  • Author(s): Kihara R
  • Journal Title: Int J Hematol. Volume: 98 Issue: 1 Pages: 98-102
  • DOI: 10.1007/s12185-012-1243-2
  • Peer Reviewed
• [Journal Article] Iron chelation therapy for a case of transfusion-independent MDS-RARS with significant iron overload. (2013)
  • Author(s): Ohashi H
  • Journal Title: Int J Hematol. Volume: 98 Issue: 1 Pages: 151-153
  • DOI: 10.1007/s12185-012-1230-7
  • Peer Reviewed
• [Journal Article] Randomized controlled trial comparing ciprofloxacin and cefepime in febrile neutropenic patients with hematological malignancies. (2013)
  • Author(s): Yasuda T
  • Journal Title: Int J Infect Dis. Volume: 17 Issue: 6 Pages: e385-e390
  • DOI: 10.1016/j.ijid.2012.12.005
  • Peer Reviewed
• [Journal Article] PROX1 overexpression inhibits protein kinase C beta II transcription through promoter DNA methylation. (2012)
  • Author(s): Hagiwara K, Ito H, Murate T, Miyata Y, Ohashi H, and Nagai H
  • Journal Title: Genes Chromosomes Cancer. Volume: 51(11) Pages: 1024-1036
• [Journal Article] Clinical characteristics of humanimmunodeficiency virus-associated Hodgkin lymphoma patients in Japan. (2012)
  • Author(s): Yotsumoto M, Hagiwara S, Ajisawa A, Tanuma J, Uehira T, Nagai H, Fujikawa Y, Maeda S, Kitano K, Arima N, Uno K, Iwai T, Hongo I, Ota Y, Fukutake K, and Okada S
  • Journal Title: Int J Hematol. Volume: 96(2) Pages: 247-53
• [Journal Article] Phase I study of BCX1777 (forodesine) in patients with relapsed or refractory peripheral T/natural killer-cell malignancies. (2012)
  • Author(s): Ogura M, Tsukasaki K, Nagai H, Uchida T, Oyama T, Suzuki T, Taguchi J, Maruyama D, Hotta T, Tobinai K
  • Journal Title: Cancer Sci. Volume: 103(7) Pages: 1290-5
• [Journal Article] Non-AIDS-defining hematological malignancies in HIV-infected patients: an epidemiological study in Japan. (2012)
  • Author(s): Hagiwara S
  • Journal Title: AIDS Volume: 27 Issue: 2 Pages: 279-283
  • DOI: 10.1097/qad.0b013e32835a5a7a
  • Peer Reviewed
• [Journal Article] PROX1 overexpression inhibits protein kinase C beta II transcription through promoter DNA methylation. (2012)
  • Author(s): Hagiwara K
  • Journal Title: Genes Chromosomes Cancer. Volume: 51 Issue: 11 Pages: 1024-1036
  • DOI: 10.1002/gcc.21985
  • Peer Reviewed
• [Journal Article] Clinical characteristics of human immunodeficiency virus-associated Hodgkin lymphoma patients in Japan. (2012)
  • Author(s): Yotsumoto M
  • Journal Title: Int J Hematol. Volume: 96 Issue: 2 Pages: 247-253
  • DOI: 10.1007/s12185-012-1127-5
  • Peer Reviewed
• [Journal Article] Phase I study of BCX1777 (forodesine) in patients with relapsed or refractory peripheral T/natural killer-cell malignancies. (2012)
  • Author(s): Ogura M
  • Journal Title: Cancer Sci. Volume: 103 Issue: 7 Pages: 1290-1295
  • DOI: 10.1111/j.1349-7006.2012.02287.x
  • Peer Reviewed
• [Journal Article] IDEC-C2B8 Study Group. Rituximab monotherapy with eight weekly infusions for relapsed or refractory patients with indolent B cell non-Hodgkin lymphoma mostly pretreated with rituximab : a multicenter phase II study. (2011)
  • Author(s): Tobinai K, Igarashi T, Itoh K, Kurosawa M, Nagai H, Hiraoka A, Kinoshita T, Uike N, Ogura M, Nawano S, Mori S, Ohashi Y
  • Journal Title: Cancer Sci. Volume: 102(9) Pages: 1698-705
• [Journal Article] Cladribine combined with rituximab (R-2-CdA) therapy is an effective salvage therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma. (2011)
  • Author(s): Nagai H, Ogura M, Kusumoto S, Takahashi N, Yamaguchi M, Takayama N, Kinoshita T, Motoji T, Ohyashiki K, Kosugi H, Matsuda S, Ohnishi K, Omachi K, Hotta T
  • Journal Title: Eur J Haematol. Volume: 86(2) Pages: 117-23
• [Journal Article] Rituximab monotherapy with eight weekly infusions for relapsed or refractory patients with indolent B cell non-Hodgkin lymphoma mostly pretreated with rituximab : a multicenter phase II study (2011)
  • Author(s): Tobinai K, Nagai H
  • Journal Title: Cancer Sci Volume: 102 Issue: 9 Pages: 1698-1705
  • DOI: 10.1111/j.1349-7006.2011.02001.x
  • Peer Reviewed
• [Journal Article] Cladribine combined with rituximab (R-2-CdA) therapy is an effective salvage therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma (2011)
  • Author(s): Nagai H.
  • Journal Title: Eur J Haematol Volume: 86 Pages: 117-123
  • Peer Reviewed
• [Journal Article] Whole brain radiation alone produces favourable outcomes for AIDS-related primary central nervous system lymphoma in the HAART era. (2010)
  • Author(s): Nagai H, Odawara T, Ajisawa A, Hagiwara S, Watanabe T, Uehira T, Uchiumi H, Yotsumoto M, Miyakawa T, Watanabe A, Kambe T, Konishi M, Saito S, Takahama S, Tateyama M, Okada S
  • Journal Title: Eur J Haematol. Volume: 84(6) Pages: 499-505
• [Journal Article] The Japanese Bendamustine Lymphoma Study Group. Multicenter phase II study of bendamustine for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. (2010)
  • Author(s): Ohmachi K, Ando K, Ogura M, Uchida T, Itoh K, Kubota N, Ishizawa K, Yamamoto J, Watanabe T, Uike N, Choi I, Terui Y, Usuki K, Nagai H, Uoshima N, Tobinai K
  • Journal Title: Cancer Sci. Volume: 101(9) Pages: 2059-64
• [Journal Article] Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells. (2010)
  • Author(s): Kubota T, Moritani S, Yoshino T, Nagai H, Terasaki H
  • Journal Title: J Clin Pathol. Volume: 63(12) Pages: 1059-65
• [Journal Article] Whole brain radiation alone produces favourable outcomes for AIDS-related primary central nervous system lymphoma in the HAART era (2010)
  • Author(s): Nagai H.
  • Journal Title: Eur J Haematol Volume: 84 Pages: 499-505
  • Peer Reviewed
• [Journal Article] Lenalidomide plus dexamethasone treatment in Japanese patients with relapsed/refractory multiple myeloma. (2010)
  • Author(s): Iisa S
  • Journal Title: Int J Hematol Volume: 92 Pages: 118-126
  • Peer Reviewed
• [Journal Article] Multicenter phase II study of bendamustine for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma. (2010)
  • Author(s): Ohmachi K
  • Journal Title: Cancer Sci Volume: 101 Pages: 2059-2064
  • Peer Reviewed
• [Journal Article] Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells (2010)
  • Author(s): Kubota K
  • Journal Title: J Clin Pathol Volume: 62 Pages: 1059-1065
  • Peer Reviewed
• [Presentation] 血液腫瘍細胞に対するベンダマスチンとキナーゼ阻害剤併用による殺細胞效果の検討 (2012)
  • Author(s): 萩原和美, 宮田泰彦, 永井宏和
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] Cytotoxicity of bendamustine combined with new gereration kinase inhibitors in lymphoid cell lines. (2012)
  • Author(s): Hagiwara K, Miyata Y, Nagai H.
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Presentation] Cytotoxic Effect of Bendamustine Combined with Kinase Inhibitors in Hematologic Cell Lines (2012)
  • Author(s): Hagiwara K
  • Organizer: 54th American Society of Hammatology
  • Place of Presentation: Atlanta, USA
• [Presentation] Phase I study of Forodesine (BCX177), an oral nucleoside phosphorylase inhibitor in patients with relapsed or refractory T/NK malignancies (2011)
  • Author(s): Maruyama D
  • Organizer: T cell lymphoma forum
  • Place of Presentation: San Francisco
  • Year and Date: 2011-01-27
• [Presentation] The mechanisms of tumor suppression by PR0X1 (2011)
  • Author(s): Hagiwara K, Murate T, Miyata Y, Hotta T, Nagai H.
  • Organizer: 第7回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] 癌抑制遺伝子としてのPROX1の機能解析 (2011)
  • Author(s): 萩原和美、村手隆、宮田泰彦、堀田知光、永井宏和
  • Organizer: 第73回日本血液学会学術集会
  • Place of Presentation: 名古屋
• [Presentation] Poorer prognosis of T/NK cell lymphoma than diffuse large B cell lymphoma in IPI low risk group contributes the unfavorable clinical outcome of T/NK cell lymphoma in clinical practice (2011)
  • Author(s): Hirokazu Nagai
  • Organizer: 11^<th> international conference on malignant lymphoma
  • Place of Presentation: Lugano, Switzerland
• [Presentation] Rituxiamb Did Not Improve Clinical Outcomes In AIDS Related Burkitt Lymphoma (2011)
  • Author(s): Hideyuki Yamamoto, Hirokazu Nagai
  • Organizer: 53^<rd> American Society of Hammatology
  • Place of Presentation: San Diego USA
• [Presentation] Prox1 suppressed tumor cell growth by the down regulation of PKCbII through the DNA methylation (2011)
  • Author(s): Kazumi Hagiwara, Hirokazu Nagai
  • Organizer: 53^<rd> American Society of Hammatology
  • Place of Presentation: San Diego USA
• [Presentation] Increased Peripheral T Cell Response to EBV-Infected Cells with Frequent Detection of EBV-DNA In Plasma and Viral mRNA In Peripheral B-Cells In Immunocompetent EBV-Positive Diffuse Large B-Cell Lymphoma Patients. (2010)
  • Author(s): Morishima S
  • Organizer: 52nd Annual Meeting of American Society of Hematology
  • Place of Presentation: Orland
  • Year and Date: 2010-12-04
• [Presentation] Durable Responses with Bendamustine Monotherapy In Patients with Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle-Cell Lymphoma (MCL) : Updated Follow-up Data From a Japanese Multicenter Phase II Study (2010)
  • Author(s): Itoh K
  • Organizer: 52nd Annual Meeting of American Society of Hematology
  • Place of Presentation: Orland
  • Year and Date: 2010-12-04
• [Presentation] 濾胞性リンパ腫-治療選択のポイント (2010)
  • Author(s): 永井宏和
  • Organizer: 第72回日本血液学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2010-09-24
• [Presentation] Poorer prognosis of intermediate BL/DLBCL compared to Burkitt lymphoma in rituximab era : A retrospective analysis with clinical and pathological features. (2010)
  • Author(s): Nagai H
  • Organizer: 15th Congress of European Hematology Association
  • Place of Presentation: Barcelona
  • Year and Date: 2010-06-10
• [Presentation] Eight weekly infusions of rituximab (R) for relapsed patients (pts) with indolent B-cell lymphoma mostly pretreated with R : A Japanese multicenter phase II study (2010)
  • Author(s): Igarashi T
  • Organizer: 46th Annual Meeting of the American Society of Clinical Oncology
  • Place of Presentation: Chicago
  • Year and Date: 2010-06-04
• [Presentation] Increased Peripheral T Cell Response to EBV-Infected Cells with Frequent Detection of EBV-DNA In Plasma and Viral mRNA In Peripheral B-Cells In Immunocompetent EBV-Positive Diffuse Large B-Cell Lymphoma Patients. (2010)
  • Author(s): Morisima S, Yamamoto K, Kimura H, Iwata S, Kinoshita T, Nagai H, Sugiura I, Tsushita K, Kagami Y, Miyamura K, Kuzushima K, Nakamura S, Morishima Y.
  • Organizer: 52th Annual Meeting of the American Society of Hematology
  • Place of Presentation: Orland, USA
• [Presentation] Proxl suppressed tumor cell growth by the down regulation of PKCbII through the DNA methylation
  • Author(s): Hagiwara K, Murate T, Miyata Y, Hotta T, Nagai H.
  • Organizer: 53^<rd> American Society of Hammatology
  • Place of Presentation: San Diego USA