Relationship of NFkB signaling and surrounding T cell co-inhibitory signaling in malignant lymphoma.

• Project/Area Number: 25461442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kobayashi Yukio 国立研究開発法人国立がん研究センター, 中央病院, 外来医長 (50240734)
• Co-Investigator(Kenkyū-buntansha): MAESHIMA Akiko 国立研究開発法人国立がん研究センター, 中央病院, 医員 (90342906) ; MUNAKATA Wataru 国立研究開発法人国立がん研究センター, 中央病院, 医員 (80601319) ; FUKUHARA Suguru 国立研究開発法人国立がん研究センター, 中央病院, 医員 (70445295) ; NOMOTO Junko 国立研究開発法人国立がん研究センター, 中央病院, 研究員 (30601322)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: DLBCL / PMBCL / Hodgkin lymphoma / NFkB / HLA / リンパ球数 / MALTリンパ腫 / ホジキンリンパ腫

Outline of Final Research Achievements

We identified prognostic impact of HLA expression on B cell lymphoma. Cases with low expression level of HLA class II had poor prognostic factor. However, cases with low expression level of Class I was not. Only those cases with low count of lymphocyte had poor prognosis.
PDL1/PDL2 expression level was examined in 34 Hodgkin lymphoma, 20 primary mediastinal large B cell lymphoma (PMBCL), and 13 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (Gray lymphoma) and classical Hodgkin lymphoma. PDL1 and PDL2 expression showed a tendency of mutually exclusive pattern; In classical Hodgkin lymphoma, PDL1 dominates, while PDL2 dominates in PMBCL. The pattern of Gray lymphoma was similar to that of Hodgkin lymphoma. The abnormality of CIITA gene was shown in only 3 cases among the total cases, and was far less frequently than previous report.

Research Products

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• [Journal Article] Clinical features and outcomes of 139 Japanese patients with Hodgkin lymphoma. (2016)
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• [Journal Article] Clinicopathological prognostic factors of 24 patients with B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. (2016)
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• [Journal Article] Classical Hodgkin lymphoma primary refractory to brentuximab vedotin, with transformation to CD30-positive diffuse large B-cell lymphoma. (2016)
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• [Journal Article] Disseminated herpes zoster infection initially presenting with abdominal pain in three lymphoma patients undergoing conventional chemotherapy. (2016)
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• [Journal Article] Phase I study of OPB-51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies. (2015)
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• [Journal Article] Intravascular large B-cell lymphoma secondary to lymphoplasmacytic lymphoma: a case report and review of literature with clonality analysis. (2015)
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• [Journal Article] Histopathological Characteristics of Lymphomas in the Upper Aerodigestive Tract: (2015)
  • Author(s): Miyagi Maeshima A, Taniguchi H, Makita S, Kitahara H, Miyamoto K, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K.
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• [Journal Article] Concurrent thymoma, thymic carcinoma, and T lymphoblastic leukemia/lymphoma in an anterior mediastinal mass. (2015)
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• [Journal Article] Phase I trial of volasertib, a Polo-like kinase inhibitor, in Japanese patients with acute myeloid leukemia. (2015)
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• [Journal Article] Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma. (2015)
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• [Journal Article] A retrospective analysis of combination chemotherapy consisting of cyclophosphamide, vincristine, prednisolone and procarbazine (C-MOPP) for pretreated aggressive non-Hodgkin lymphoma. (2015)
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• [Journal Article] Clinicopathological features of classical Hodgkin lymphoma in patients ≧ 40 years old, with special reference to composite cases. (2015)
  • Author(s): Maeshima AM, Taniguchi H, Nomoto J, Makita S, Kitahara H, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K.
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• [Journal Article] Incidental detection of malignant lymphoma in subjects in a cancer surveillance programme. (2015)
  • Author(s): Kamiyama Y, Kobayashi Y, Fukuhara S, Morikawa N, Munakata W, Miyagi Maeshima A, Maruyama D, Kim SW, Watanabe T, Terauchi T, Muramatsu Y, Tobinai K.
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• [Journal Article] A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia (2015)
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• [Journal Article] Histopathological analysis of B-cell non-Hodgkin lymphomas without light chain restriction by using flow cytometry. (2015)
  • Author(s): Ohmoto A, Maeshima AM, Taniguchi H, Tanioka K, Makita S, Kitahara H, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K.
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• [Journal Article] Positive impact of chronic graft-versus-host disease on the outcome of patients with de novo myelodysplastic syndrome after allogeneic hematopoietic cell transplantation: a single-center analysis of 115 patients. (2014)
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  • Journal Title: Eur J Haematol. Volume: 92 Issue: 2 Pages: 137-146
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• [Journal Article] Japan Clinical Oncology Group (JCOG) prognostic index and characterization of long-term survivors of aggressive adult T-cell leukaemia-lymphoma (JCOG0902A). (2014)
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• [Journal Article] Prognostic significance of immunophenotypes and a nodular pattern in primary mediastinal large B-cell lymphoma. (2014)
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• [Journal Article] Prognostic biomarkers in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy. (2014)
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  • Journal Title: Cancer Sci Volume: 105 Issue: 11 Pages: 1435-1441
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• [Journal Article] Tamibarotene As Maintenance Therapy for Acute Promyelocytic Leukemia: Results From a Randomized Controlled Trial. (2014)
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  • Journal Title: J Clin Oncol. Volume: 32 Issue: 33 Pages: 3729-3735
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• [Journal Article] Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group. (2014)
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  • Journal Title: Blood Cancer Journal Volume: 4 Issue: 10 Pages: 252-252
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• [Journal Article] Clinicopathological characteristics of follicular lymphoma with peripheral blood involvement. (2014)
  • Author(s): Maeshima AM, Taniguchi H, Tanioka K, Kitahara H, Miyamoto KI, Fukuhara S, Munakata W, Suzuki T, Maruyama D, Kobayashi Y, Tobinai K, Kushima R.
  • Journal Title: Leuk Lymphoma. Volume: 14 Issue: 7 Pages: 1-5
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• [Journal Article] Intrafollicular classical Hodgkin lymphoma mimicking nodular lymphocyte predominant Hodgkin lymphoma: A report of two cases. (2014)
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• [Journal Article] Normal karyotype acute myeloid leukemia with the CD7+ CD15+ CD34+ HLA-DR + immunophenotype is a clinically distinct entity with a favorable outcome. (2014)
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  • Journal Title: Ann Hematol Volume: in press Issue: 6 Pages: 957-963
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• [Journal Article] Follow-up Data of 10 Patients With B-cell Non-Hodgkin Lymphoma With a CD20-negative Phenotypic Change After Rituximab-containing Therapy. (2013)
  • Author(s): Maeshima AM, Taniguchi H, Fukuhara S, Morikawa N, Munakata W, Maruyama D, Kim SW, Watanabe T, Kobayashi Y, Tobinai K, Tsuda H.
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• [Journal Article] Phase 2 study of arsenic trioxide followed by autologous hematopoietic cell transplantation for relapsed acute promyelocytic leukemia. (2013)
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  • Journal Title: Blood Volume: 121 Issue: 16 Pages: 3095-3012
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• [Journal Article] Ewing sarcoma arising after treatment of diffuse large B-cell lymphoma (2013)
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• [Journal Article] A20 (TNFAIP3) Deletion in Epstein-Barr Virus-Associated Lymphoproliferative Disorders/Lymphomas. (2013)
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• [Journal Article] Clinicopathological prognostic indicators in 107 patients with diffuse large B-cell lymphoma transformed from follicular lymphoma. (2013)
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• [Journal Article] Epstein-Barr virus-associated enteropathy as a complication of infectious mononucleosis mimicking peripheral T-cell lymphoma. (2013)
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• [Journal Article] The demarcation between younger and older acute myeloid leukemia patients. (2013)
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• [Journal Article] A retrospective study of 5-year outcomes of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma refractory to Helicobacter pylori eradication therapy. (2013)
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• [Journal Article] Prognostic implications of histologic grade and intensity of Bcl-2 expression in follicular lymphomas undergoing rituximab-containing therapy. (2013)
  • Author(s): Maeshima, A.M, Taniguchi H, Nomoto J, Miyamoto K, Fukuhara S, Munakata W, Maruyama D, Kim SW, Watanabe T, Kobayashi Y, Tobinai K, Tsuda H.
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• [Presentation] PDL1, PDL2 expression in classical Hodgkin lymphoma, primary mediastinal large B cell lymphoma, and lymphoma with intermediate characteristics between classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma (2016)
  • Author(s): Yosuke Tanaka, Akiko Miyagi Maeshima, Junko Nomoto, Shinichi Makita, Suguru Fukuhara, Wataru Munakata, Dai Maruyama, Kensei Tobinai, Yukio Kobayashi
  • Organizer: American Society of Hematology, Lymphoma Biology
  • Place of Presentation: Colorado Springs, CO, USA
  • Year and Date: 2016-06-18
  • Int'l Joint Research
• [Book] 造血器腫瘍診療ガイドライン2013年版 (2013)
  • Author(s): 小林幸夫ほか、（一般社団法人 日本血液学会編）
  • Publisher: 金原出版