BIOLOGICAL ROLE OF CHROMOSOME TRANSLOCATION JUNCTION REGION GENES IN HEMATOPOIETIC CELL DIFFERENTIATION AND PROLIFERATION

染色体易位连接区基因在造血细胞分化和增殖中的生物学作用

• 批准号: 08457282
• 负责人: SETO Masao
• 金额: $ 5.18万
• 依托单位: AICHI CANCER CENTER
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457282/
• 关键词: LYMPHOMA; Hematopoietic malignancy; cyclin D1; BCL1; BCL2; BCL6; MLL; MALT lymphoma; cyclin D2; cyclin D3

A specific chromosome translocation is recurrently found in a specific type of hematologic malignancy and the translocation junction region genes have been recognized to play and important role in hematopoietic cell differentiation and proliferation. Our research for three years produced following results.1. MLL gene associated with infantile leukemia and therapy-related leukemiaWe produced the specific antibody against N-terminal MLL recombinant protein and showed that the MLL product is localized in nuclei. We also showed that the MLL-partner chimeric products localize in nuclei irrespective of translocation partner genes. We succeeded in establishing leukemia cell lines which can express MLL-LTG9 chimeric product, the most common type of therapy-related leukemia, upon IPTG induction. Using this system, we demonstrated that Hox-a7, b7, c9 are the target for chimeric MLL products.2. BCLl/cyclin Dl gene on 11q13 chromosome translocation junction region :We established the specific mono … More clonal antibody, 5D4, which can immuno-stan formalin-fixed, paraffin-embedded tissues. Importantly, we have shown that the positive staining reflected overexpression of cyclin Dl. We have examined 151 cases of mantle cell lymphoma (MCL) and found that 85% showed positive staining. Furthermore, the negative group of MCL has been shown to be a group with good prognosis distinct from the positive group of MCL, indicating the immunostaining is very important in selecting therapy strategy.3. Diffuse large B-cell lymphoma (DLBL) and mucosa-associated lymphoid tissue (MALI) lymphoma :DLBL constitutes of heterogeneous subtypes of B-cell lymphoma. We could identify three groups based on immunophenotype. Major translocation junction genes in B-cell lymphoma development are BCLl, BCL2, and BCL6, but gene rearrangement of these genes failed to identify any unique subtypes. MALT lymphoma has similar immunophenotype with DLBL, and we are trying to disclose 18q2 1 translocation junction genes which also should be useful in dissecting DLBL. Less

特定的染色体易位是一种特定类型的血液性恶性肿瘤，并且在造血细胞的分化和增殖中被认为发挥作用和重要作用。重组和显示MLL粉尘位于核中。系统，我们证明了HOX-A7，B7，C9是嵌合MLL产物的目标，我们已经表明，阳性染色反映了Cyclin dl的过表达，我们检查了151个CASSES斑壁细胞淋巴瘤（MCL），发现85％的MCL表现为阳性。进口策略3。亚型。麦芽淋巴瘤与DLBL具有相似的免疫表型，我们试图披露18q2 1的易位连接基因，这也应在于较少的DLBL

项目成果

Taki, T.et al.: "Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia." 1303-1307 (1996)

Taki, T. 等人：“婴儿急性白血病中 MLL 基因重排的频率和临床意义。”

Ohshima,A.: "11q23 aberration is an additional chromosomal change in de nove acute leukemia after treatment with etoposide and mitoxantrone." American J.Hematol.53. 264-266 (1996)

Ohshima,A.：“11q23 畸变是新发急性白血病在依托泊苷和米托蒽醌治疗后出现的额外染色体变化。”

Kitazawa, J.et al: "Progression from myelodysplastic syndrome with monosomy 7 to acute monoblastic leukemta with MLL gene rearrangement." Int. J.Hematol.67. 23-26 (1998)

Kitazawa, J. 等人：“从 7 号单体性骨髓增生异常综合征进展为 MLL 基因重排的急性单核细胞白血病。”

Tomita, A.et al.: "Truncated e-Myb expression in the human leukemia cell line TK-6." Leukemia. 12. 1422-1429 (1998)

Tomita, A.等人：“人白血病细胞系 TK-6 中 e-Myb 的表达被截断。”

Taki, T., et al.: "Frequency and clinical significance of the MLL gene rearrangements in infant acute leukemia." Leukemia. 10. 1303-1307 (1996)

Taki, T. 等人：“婴儿急性白血病中 MLL 基因重排的频率和临床意义。”