2001 Fiscal Year Annual Research Report

悪性リンパ腫におけるMALT1とAPI2遺伝子発現の意義の病理学的、生物学的研究

Research Project

Project/Area Number	12670191
Research Institution	Aichi Cancer Center Research Institute
Principal Investigator	中村栄男愛知県がんセンター, 研究所, 研究員 (80180363)
Keywords	悪性リンパ腫 / MALTリンパ腫 / t(11;18)染色体転座 / API2 / MALT1 / キメラ遺伝子 / Helicobacter pylori / 除菌療法
Research Abstract	節外性リンパ腫の中心をなす粘膜関連リンパ組織型B細胞リンパ腫(MALTリンパ腫)は発生頻度が高く、明確な疾患単位を形成する。しかし、その腫瘍発生での分子病態の解明は不明のままであった。我々は、t(11;18)染色体転座がMALTリンパ腫の原因の一つである可能性を報告してきた。そして外科的手術材料を用いてt(11;18)切断点を世界に先駆けて公表した。さらに18番染色体上の責任遺伝子の同定に成功し、未知の遺伝子であることからMALT1と命名した。一方、11番染色体上の遺伝子は既知のAPI2であった。t(11;18)染色体転座によるAPI2-MALT1キメラ遺伝子の形成が、MALTリンパ腫の発生に深く関わるものと推定された。当該研究期間中にRT-PCR法あるいはFISH法を用いてAPI2-MALT1キメラ遺伝子のパラフィン切片からの検出システムを開発すると共に、その医学的意義についての解明を進めた。その結果、胃MALTリンパ腫においてはAPI2-MALT1キメラ遺伝子の検出がHelicobacter pylori除菌療法に対するMALTリンパ腫の反応性を予測し得る分子マーカーであることを初めて明らかにした。一方、これら有為なデータの解析において強力な臨床治療研究グループとの提携が不可欠であった。また、それら治療研究グループの育成と連携において、本邦は欧米に比べて未だ立ち遅れた状況にあることが痛感された。今後の研究の展開を計る上での幾つかの課題を残した研究期間であったとも云える。

Research Products

(38 results)

All Other

All Publications (38 results)

[Publications] Yamaguchi M, et al.: "De novo CD5-positive diffuse large B-cell lymphoma : a clinicopathologic study of 109 partienrs"Blood. 99. 815-821 (2002)
[Publications] Kojima M, et al.: "Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers : a clinicopathological and immunohistochemical study of 10 cases"APMIS. 109. 699-706 (2001)
[Publications] Kojima M, et al.: "Marginal zone B cell lymphomas of Waldeyer's ring : a report of two tonsillectomy case resembling histomorphological features of inflammatory lesions"Pathol Res Pract. 197. 781-784 (2001)
[Publications] Japan Lymphoma Radiation Therapy Group: "Localized aggressive nonHodgkin's lymphoma of the nasal cavity : a survey by the Japan Lymphoma Radiation Therapy Group"Int J Radiation Oncology Biol Phys. 51. 1228-1233 (2001)
[Publications] Kojima M, et al.: "Inflammatory pseudotumor of lymph nodes : clinicopathologic and immunohistological study of 11 Japanese cases"Int J Surg Pathol. 9. 207-214 (2001)
[Publications] Takahashi N, et al.: "A clinicopathological study of 20 patients with T/natural (NK)-cell lymphoma-associated hemophagocytic syndrome with special reference to nasal-type NK/T-cell lymphoma"Int J Hematol. 74. 303-308 (2001)
[Publications] Hara Y, et al.: "Intraclonal microheterogeneity of mucosa-associated lymphoid tissue lymphoma with a multiple lymphomatous polyposis appearance in the gastrointestinal tract"Pathol Int. 51. 744-746 (2001)
[Publications] Yatabe Y, et al.: "Morphologic Spectrum of Cyclin D1-Positive Mantle Cell Lymphoma : A Study of 168 Cases"Pathol Int. 51. 747-761 (2001)
[Publications] Kato M, et al.: "Pregnancy-associated cytotoxic lymphoma : a report of 4 cases"Int J Hematol. 74. 186-192 (2001)
[Publications] Tamura A, et al.: "Interphase detection of immunoglobulin heavy chain translocations with specific oncogene loci in 173 patients with B-cell lymphoma"Cancer Genet Cytogenet. 129. 1-9 (2001)
[Publications] Matsuo K, et al.: "No substantial difference in genotype frequencies of interleukin and myeloperoxidase polymorphisms between malignant lymphoma patients and non-cancer controls"Haematologica. 86. 602-608 (2001)
[Publications] Kojima M, et al.: "Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma : a clinicopathologic study of nine cases"APMIS. 109. 419-427 (2001)
[Publications] Kojima M, et al.: "Lymph node necrosis in systemic lupus erythematosus : a histopathological and immunohistochemical study of four cases"APMIS. 109. 141-146 (2001)
[Publications] Yonezumi M, et al.: "Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription PCR and genomic long and accurate PCR analyses"Br J Haematol. 115. 588-594 (2001)
[Publications] Suzuki R, et al.: "Detection of cyclin D1 overexpression by real-time reverse-transcriptase-mediated quantitative polymerase chain reaction for the diagnosis of mantle cell lymphoma"Am J Pathol. 159. 425-429 (2001)
[Publications] Kojima M, et al.: "Inflammatory pseudotumor of the submandibular gland : report of a case presenting with autoimmune disease-like clinical manifestations"Arch Pathol Lab Med. 125. 1095-1097 (2001)
[Publications] Toyoda H, et al.: "Regression of primary lymphoma of the ampulla of Vater after eradication of Helicobacter pylori"Gastrointest Endosc. 54. 92-96 (2001)
[Publications] Suzuki R, et al.: "Sarcomatoid variant of anaplastic large cell lymphoma with cytoplasmic ALK and α-smooth muscle actin expression a mimic of inflammatory myofibroblastic tumor"Am J Pathol. 159. 383-384 (2001)
[Publications] Sugiyama T, et al.: "API2-MALT1 chimeric transcript is a predictive marker for the responsiveness of H. pylori eradication treatment in low-grade gastric MALT lymphoma"Gastroenterology. 120. 1884-1885 (2001)
[Publications] Kojima M, et al.: "Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles"Pathol Res Pract. 197. 237-244 (2001)
[Publications] Kondo E, et al.: "Assessment of prognostic factors in follicular lymphoma patients"Int J Hematol. 73. 363-368 (2001)
[Publications] Matsuo K, et al.: "Association between polymorphisms of folate-and methionine-metabolizing enzymes and susceptibility to malignant lymphoma"Blood. 97. 3205-3209 (2001)
[Publications] Kagami Y, et al.: "Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular dendritic cell-like cell line HK"Leukemia. 15. 148-156 (2001)
[Publications] Inagaki H, et al.: "API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma : Multiplex RT-PCR detection using formalin-fixed paraffin specimens"Am J Pathol. 158. 699-706 (2001)
[Publications] Nakamura S, et al.: "Peripheral T/NK-cell lymphoma involving the female genital tract : a clinicopathologic study of 5 cases"Int J Hematol. 73. 108-114 (2001)
[Publications] Isobe K, et al.: "Blastic natural killer cell lymphoma arising from the mediastinum with terminal deoxynucleotidyl transferase expression"Pathol Int. 51. 55-59 (2001)
[Publications] Miura I, et al.: "Detection of t(14;18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease"Cancer Genet Cytogenet. 123. 97-101 (2000)
[Publications] Murase T, et al.: "An Asian variant of intravascular large B-cell lymphoma : clinical, pathological and cytogenetic approaches to DLBCL associated with haemophagocytic syndrome"Br J Haematol. 111. 826-834 (2000)
[Publications] Yamashita Y, et al.: "Lennert's lymphoma-a variant of cytotoxic T-cell lymphoma?"Am J Surg Pathol. 24. 1627-1633 (2000)
[Publications] Suzuki R, et al.: "Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype"Blood. 96. 2993-3000 (2000)
[Publications] Nakamura T, et al.: "The t(11;18)(q21;q21) translocation in H. pylori-negative low-grade gastric MALT lymphoma"Am J Gastroenterol. 11. 3314-3315 (2000)
[Publications] Murata T, et al.: "Granzyme B-positive primary gastric T-cell lymphoma gastric T-cell lymphoma with the possibility of extrathymic T-cell origin"Pathol Int. 50. 853-857 (2000)
[Publications] Nagasaka T, et al.: "Anaplastic large cell lymphomas presented as bone lesions : a clinicopathologic study of six cases and review of the literature"Mod Pathol. 13. 1143-1149 (2000)
[Publications] Nakamura S, et al.: "'Hallmark' cells in nodal cytotoxic lymphomas-response"Am J Surg Pathol. 24. 1310 (2000)
[Publications] Lymphoma study group of Japanese pathologists: "The World Health Organization classification of malignant lymphomas in Japan : incidence of recently recognized entities"Pathol Int. 50. 696-702 (2000)
[Publications] Yatabe Y, et al.: "Topographical distributions of allelic loss in individual non-small-cell lung cancers"Am J Pathol. 157. 985-993 (2000)
[Publications] Kodera Y, et al.: "Primary Gastric B Cell Lymphoma : Audit of 82 Cases Treated with Surgery and Classified According to the Concept of Mucosa-associated Lymphoid Tissue Lymphoma"World J Surg. 24. 857-862 (2000)
[Publications] Kojima M, et al.: "Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients : a clinicopathological and immunohistological study of 21 cases"Pathol Int. 50. 304-312 (2000)

2001 Fiscal Year Annual Research Report

悪性リンパ腫におけるMALT1とAPI2遺伝子発現の意義の病理学的、生物学的研究

Principal Investigator

中村 栄男 愛知県がんセンター, 研究所, 研究員 (80180363)

Research Products

[Publications] Yamaguchi M, et al.: "De novo CD5-positive diffuse large B-cell lymphoma : a clinicopathologic study of 109 partienrs"Blood. 99. 815-821 (2002)

[Publications] Kojima M, et al.: "Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers : a clinicopathological and immunohistochemical study of 10 cases"APMIS. 109. 699-706 (2001)

[Publications] Kojima M, et al.: "Marginal zone B cell lymphomas of Waldeyer's ring : a report of two tonsillectomy case resembling histomorphological features of inflammatory lesions"Pathol Res Pract. 197. 781-784 (2001)

[Publications] Japan Lymphoma Radiation Therapy Group: "Localized aggressive nonHodgkin's lymphoma of the nasal cavity : a survey by the Japan Lymphoma Radiation Therapy Group"Int J Radiation Oncology Biol Phys. 51. 1228-1233 (2001)

[Publications] Kojima M, et al.: "Inflammatory pseudotumor of lymph nodes : clinicopathologic and immunohistological study of 11 Japanese cases"Int J Surg Pathol. 9. 207-214 (2001)

[Publications] Takahashi N, et al.: "A clinicopathological study of 20 patients with T/natural (NK)-cell lymphoma-associated hemophagocytic syndrome with special reference to nasal-type NK/T-cell lymphoma"Int J Hematol. 74. 303-308 (2001)

[Publications] Hara Y, et al.: "Intraclonal microheterogeneity of mucosa-associated lymphoid tissue lymphoma with a multiple lymphomatous polyposis appearance in the gastrointestinal tract"Pathol Int. 51. 744-746 (2001)

[Publications] Yatabe Y, et al.: "Morphologic Spectrum of Cyclin D1-Positive Mantle Cell Lymphoma : A Study of 168 Cases"Pathol Int. 51. 747-761 (2001)

[Publications] Kato M, et al.: "Pregnancy-associated cytotoxic lymphoma : a report of 4 cases"Int J Hematol. 74. 186-192 (2001)

[Publications] Tamura A, et al.: "Interphase detection of immunoglobulin heavy chain translocations with specific oncogene loci in 173 patients with B-cell lymphoma"Cancer Genet Cytogenet. 129. 1-9 (2001)

[Publications] Matsuo K, et al.: "No substantial difference in genotype frequencies of interleukin and myeloperoxidase polymorphisms between malignant lymphoma patients and non-cancer controls"Haematologica. 86. 602-608 (2001)

[Publications] Kojima M, et al.: "Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma : a clinicopathologic study of nine cases"APMIS. 109. 419-427 (2001)

[Publications] Kojima M, et al.: "Lymph node necrosis in systemic lupus erythematosus : a histopathological and immunohistochemical study of four cases"APMIS. 109. 141-146 (2001)

[Publications] Yonezumi M, et al.: "Detection of AP12-MALT1 chimaeric gene in extranodal and nodal marginal zone B-cell lymphoma by reverse transcription PCR and genomic long and accurate PCR analyses"Br J Haematol. 115. 588-594 (2001)

[Publications] Suzuki R, et al.: "Detection of cyclin D1 overexpression by real-time reverse-transcriptase-mediated quantitative polymerase chain reaction for the diagnosis of mantle cell lymphoma"Am J Pathol. 159. 425-429 (2001)

[Publications] Kojima M, et al.: "Inflammatory pseudotumor of the submandibular gland : report of a case presenting with autoimmune disease-like clinical manifestations"Arch Pathol Lab Med. 125. 1095-1097 (2001)

[Publications] Toyoda H, et al.: "Regression of primary lymphoma of the ampulla of Vater after eradication of Helicobacter pylori"Gastrointest Endosc. 54. 92-96 (2001)

[Publications] Suzuki R, et al.: "Sarcomatoid variant of anaplastic large cell lymphoma with cytoplasmic ALK and α-smooth muscle actin expression a mimic of inflammatory myofibroblastic tumor"Am J Pathol. 159. 383-384 (2001)

[Publications] Sugiyama T, et al.: "API2-MALT1 chimeric transcript is a predictive marker for the responsiveness of H. pylori eradication treatment in low-grade gastric MALT lymphoma"Gastroenterology. 120. 1884-1885 (2001)

[Publications] Kojima M, et al.: "Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles"Pathol Res Pract. 197. 237-244 (2001)

[Publications] Kondo E, et al.: "Assessment of prognostic factors in follicular lymphoma patients"Int J Hematol. 73. 363-368 (2001)

[Publications] Matsuo K, et al.: "Association between polymorphisms of folate-and methionine-metabolizing enzymes and susceptibility to malignant lymphoma"Blood. 97. 3205-3209 (2001)

[Publications] Kagami Y, et al.: "Establishment of a follicular lymphoma cell line (FLK-1) dependent on follicular dendritic cell-like cell line HK"Leukemia. 15. 148-156 (2001)

[Publications] Inagaki H, et al.: "API2-MALT1 fusion transcripts involved in mucosa-associated lymphoid tissue lymphoma : Multiplex RT-PCR detection using formalin-fixed paraffin specimens"Am J Pathol. 158. 699-706 (2001)

[Publications] Nakamura S, et al.: "Peripheral T/NK-cell lymphoma involving the female genital tract : a clinicopathologic study of 5 cases"Int J Hematol. 73. 108-114 (2001)

[Publications] Isobe K, et al.: "Blastic natural killer cell lymphoma arising from the mediastinum with terminal deoxynucleotidyl transferase expression"Pathol Int. 51. 55-59 (2001)

[Publications] Miura I, et al.: "Detection of t(14;18)(q32;q21) in hyperdiploid cells by fluorescence in situ hybridization in a patient with Hodgkin disease"Cancer Genet Cytogenet. 123. 97-101 (2000)

[Publications] Murase T, et al.: "An Asian variant of intravascular large B-cell lymphoma : clinical, pathological and cytogenetic approaches to DLBCL associated with haemophagocytic syndrome"Br J Haematol. 111. 826-834 (2000)

[Publications] Yamashita Y, et al.: "Lennert's lymphoma-a variant of cytotoxic T-cell lymphoma?"Am J Surg Pathol. 24. 1627-1633 (2000)

[Publications] Suzuki R, et al.: "Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype"Blood. 96. 2993-3000 (2000)

[Publications] Nakamura T, et al.: "The t(11;18)(q21;q21) translocation in H. pylori-negative low-grade gastric MALT lymphoma"Am J Gastroenterol. 11. 3314-3315 (2000)

[Publications] Murata T, et al.: "Granzyme B-positive primary gastric T-cell lymphoma gastric T-cell lymphoma with the possibility of extrathymic T-cell origin"Pathol Int. 50. 853-857 (2000)

[Publications] Nagasaka T, et al.: "Anaplastic large cell lymphomas presented as bone lesions : a clinicopathologic study of six cases and review of the literature"Mod Pathol. 13. 1143-1149 (2000)

[Publications] Nakamura S, et al.: "'Hallmark' cells in nodal cytotoxic lymphomas-response"Am J Surg Pathol. 24. 1310 (2000)

[Publications] Lymphoma study group of Japanese pathologists: "The World Health Organization classification of malignant lymphomas in Japan : incidence of recently recognized entities"Pathol Int. 50. 696-702 (2000)

[Publications] Yatabe Y, et al.: "Topographical distributions of allelic loss in individual non-small-cell lung cancers"Am J Pathol. 157. 985-993 (2000)

[Publications] Kodera Y, et al.: "Primary Gastric B Cell Lymphoma : Audit of 82 Cases Treated with Surgery and Classified According to the Concept of Mucosa-associated Lymphoid Tissue Lymphoma"World J Surg. 24. 857-862 (2000)

[Publications] Kojima M, et al.: "Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients : a clinicopathological and immunohistological study of 21 cases"Pathol Int. 50. 304-312 (2000)

中村栄男愛知県がんセンター, 研究所, 研究員 (80180363)