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

在特定类型的恶性血液病中经常发现特定的染色体易位，并且易位连接区基因已被认为在造血细胞分化和增殖中起重要作用。我们经过三年的研究，得出以下结果。MLL基因与婴儿白血病和治疗相关性白血病的关系我们制备了抗N端MLL重组蛋白的特异性抗体，并证明MLL产物定位于细胞核。我们还表明，MLL-伴侣嵌合产物定位于细胞核中，而与易位伴侣基因无关。我们成功地建立了白血病细胞系，其可以在IPTG诱导后表达MLL-LTG 9嵌合产物，这是最常见的治疗相关白血病类型。使用该系统，我们证明了Hox-a7，b7，c9是嵌合MLL产物的靶点. 11 q13染色体易位连接区的BCL 1/cyclin D1基因：我们建立了特异性的单克隆抗体， 关于我们 克隆抗体5D4，可免疫固定福尔马林固定、石蜡包埋组织。重要的是，我们已经表明阳性染色反映了细胞周期蛋白D1的过表达。本文报告151例套细胞淋巴瘤（MCL），阳性率为85%。此外，与阳性组相比，阴性组预后较好，提示免疫组化在选择治疗策略中具有重要意义.弥漫性大B细胞淋巴瘤（DLBL）和粘膜相关淋巴组织（MALI）淋巴瘤：DLBL由异质性B细胞淋巴瘤亚型组成。我们可以根据免疫表型将其分为三组。B细胞淋巴瘤发展中的主要易位连接基因是BCL 1、BCL 2和BCL 6，但这些基因的基因重排未能鉴定出任何独特的亚型。MALT淋巴瘤与DLBL具有相似的免疫表型，我们试图揭示18 q21易位连接基因，这也将有助于DLBL的解剖。少

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