節外性リンパ腫発生の分子病態の解明を目指した病理学的、分子生物学的研究

1999 Fiscal Year Annual Research Report

• Project/Area Number: 10670188
• Research Institution: Aichi Cancer Center
• Principal Investigator: 中村 栄男 愛知県がんセンター, 研究所, 研究員 (80180363)
• Keywords: Malignant lymphoma / Extranodal lymphoma / MALT lymphoma / t(11;18)(q21;q21) / API2 / MALT1 / Pathology / Molecular biology

Research Abstract

悪性リンパ腫は極めて多様性に富む腫瘍であり、その本態の解明は真に学際的な研究によってのみ可能である。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IsaacsonとWrightにより1983年に提唱された。当初、その本態に関して強い懐疑論に晒されたが、最近提案されたREAL分類さらに現在成案中の新WHO分類では独立項目として掲載されている。本邦非ホジキンリンパ腫全体の約16%を占め、明確な疾患単位を形成する。しかし、その腫瘍発生における分子病態は長く解明されないままであった。我々は本腫瘍発生への関与が推定されるt(11;18)染色体転座を有するMALTリンパ腫の報告を重ねた。これら腫瘍の外科的手術材料を用いてFISH法等の細胞遺伝学的および分子生物学的手法によりt(11;18)切断点を世界に先駆けて公表した(1999年2月)。さらに18番染色体上のtarget遺伝子のクローニングによる同定に成功し、新たな遺伝子であることよりMALT1と命名した(1999年10月)。また、11番染色体上の遺伝子は既知のAPI2であった。これら遺伝子の医学的重要性が強く示唆される。しかし、それらのヒトにおける病理学的、生物学的意義は現段階では全く不明であると云わざるをえない。今後、FISH、PCR、Northern法などを駆使して悪性リンパ腫におけるMALT1とAPI2遺伝子発現と異常の全体像の解明を目指すことは急務である。さらに検討対象をヒト腫瘍全体へ展開し、免疫系における生理学的役割という視点からのアプローチも必要とされよう。

Research Products

• [Publications] Yatabe Y., et al.: "Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma (MCL) : a clinico-"Blood. (in press). (2000)
• [Publications] Motegi M., et al.: "API2-MALT1 chimeric transcripts involved in mucosaassociated lymphoid tissue type lymphoma predict"Am J Pathol. (in press). (2000)
• [Publications] Suzuki R., et al.: "Idiopathic eosinophilia and adult T-cell leukemia"N Engl J Med. 342. 660 (2000)
• [Publications] Takahashi, H., et al.: "Infrequent BCL10 mutations in B-cell non-Hodgkin's lymphomas"Jpn J Cancer Res. 90. 1316-1320 (1999)
• [Publications] Kagami Y., et al.: "Nodal cytotoxic lymphoma. A clinicopathologic study of 66 cases"Am J Surg Pathol. 23. 1184-1200 (1999)
• [Publications] Akagi T., et al.: "A novel genr, MALT1 at 18q21, is involved in t (11;18) (q21;q21) found in low-grade B-cell lymphoma of MALT"Oncogene. 18. 5785-5794 (1999)
• [Publications] Yokoi T., et al.: "Primary low-grade gastric MALT lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma : a clinico-"Pathol Int. 49. 702-709 (1999)
• [Publications] Suzuki R., et al.: "Selective usage of D-type cyclins in lymphoid malignancies"Leukemia. 13. 1335-1342 (1999)
• [Publications] Harada S., et al.: "Molecular and immunological dissection of diffuse large B cell lymphoma : CD5+, and CD5- with CD10+ groups"Leukemia. 13. 1441-1447 (1999)
• [Publications] Matano S., et al.: "Monomorphic agranular natural killer cell lymphoma/leukemia with no Epstein-Barr virus"Acta Haematol. 101. 206-208 (1999)
• [Publications] Yazaki M., et al.: "A novel minor histocompatibility antigen recognized by HLA-A31 restricted cytotoxic T lymphocytes generated"Bone Marrow Transplantation. 24. 129-137 (1999)
• [Publications] Hosaka S., et al.: "MALT-type lymphoma of the rectum with chromosomal translocation of the t(11;18) (q21;q21) and an additional"Am J Gastroenterol. 94. 1951-1954 (1999)
• [Publications] Kuzushima K., et al.: "Increased frequency of antigen-specific CD8+ cytotoxic T lymphocytes infiltrating an Epstein-Barr virus-associated"J Clin Invest. 104. 163-171 (1999)
• [Publications] Suzuki S. & Nakamura S.: "Malignancies of NK cell precursor : myeloid/NK cell precursor acute leukemia and blastic NK cell lymphoma"Leuk Res. 23. 615-624 (1999)
• [Publications] Murase T & Nakamura S: "An asian variant of intravascular lymphomatosis : a review"Leuk Lymphoma. 33. 459-473 (1999)
• [Publications] Nakamura S., et al.: "hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker : a clinico-"Am J Surg Pathol. 23. 363-376 (1999)
• [Publications] Akagi T., et al.: "Molecular cytogenetic delineation of the breakpoint at 18q21.lin low-qrade B-cell lymphoma of MALT"Genes Chromosomes Cancer. 24. 315-321 (1999)
• [Publications] Yufu Y., et al.: "A new multiple myeloma cell line, MEF-1, possesses cyclin D1 overexpression and the p53 mutation"Cancer. 85. 1750-1757 (1999)
• [Publications] Inoue M., et al.: "Infulence of habitual smoking on gastric cancer by histologic subtype"Int J Cancer. 81. 39-43 (1999)
• [Publications] Murase T., et al.: "Blast crisis of chronic myelogeneous leukemia exhibiting immunophenotypic features of a myloid/NK precursor"Int J Hematol. 69. 89-91 (1999)
• [Publications] Kagami Y., et al.: "Establishment of an IL-2-dependent cell line derived from 'nasal-type' NK/T-cell lymphoma"Br J Haematol. 103. 669-677 (1998)
• [Publications] Fonbseca R., et al.: "Follicular dendritic cell sarcoma and interdigitating reticulum cell sarocoma : a review"Am J Hematol. 59. 161-167 (1998)
• [Publications] Kojima M., et al.: "imprint cytology of large B-cell lymphoma with high content of epithelioid cells"Pathol Res Pract. 194. 559-565 (1998)
• [Publications] Murase T., et al.: "Detection of antibodies to Fasciola and Anisakis in Japanese patients with intravascular lymphomatosis"Blood. 92. 2182-2183 (1998)
• [Publications] Kojima M., et al.: "Occurrence of monocytoid B-cells in reactive lymph node lesion"Pathol Res Pract. 194. 559-565 (1998)
• [Publications] Kojima M., et al.: "Florid reactive follicular hyperplasia in elderily patients. A clinicopathologic study of 23 cases"Pathol Res Pract. 194. 391-398 (1998)
• [Publications] Tamura A., et al.: "Delineation of the breakpoint at 18q21.1 in a cell line (Karpas 1106) derived from mediastinal B-cell"Int J Cancer. 78. 100-105 (1998)
• [Publications] Hosokawa Y., et al.: "A small deletion in the 3'-untranslated region of the cyclin D1/PRAD1/BCL-1 oncogene in a patient with CLL"Int J Cancer. 76. 791-796 (1998)
• [Publications] Mitsuoka C., et al.: "Identification of a major carbohydrate capping group of the L-selection ligand on high endothelial venules"J Biol Chem. 273. 11225-11233 (1998)
• [Publications] Suzuki R., et al.: "Importance of T-cell receptor delta-chain gene analysis on CD7+ and CD56+ myeloid/NK cell precursor leukemia"Blood. 91. 2623-2624 (1998)