TRANSLOCATION OF 8-13 IN STEM-CELL LEUKEMIA/LYMPHOMA

一种新的干细胞白血病/淋巴瘤，涉及T细胞，B细胞， 在过去的三年里，人们已经描述了髓系血统。多数 有外周淋巴结病和淋巴活检的患者 典型表现为T细胞淋巴母细胞性淋巴瘤。伴生骨髓 另一方面，活组织检查通常显示髓系增生。 明显的嗜酸性粒细胞增多症。淋巴瘤对治疗反应良好，但大多数 患者进展为全面、迅速致命的急性骨髓性 白血病。值得注意的是，患有这种综合征的患者具有平衡性 相互易位，涉及染色体带8p11和13q11-12， 淋巴瘤性周围结节和骨髓增生性病变 骨髓细胞。这一观察表明易位(8；13)是 多潜能细胞中的一个关键致癌事件 髓系和淋巴系分化。我们已经绘制了移位图 (8；13)使用分子细胞遗传学方法的断点 将8p断裂点定位于70kb的细菌人工染色体 (BAC)克隆。我们初步的BAC基因筛选研究表明 FGFRI是易位(；13)的候选基因。我们假设 易位8p断裂点的基因是致癌的 通过与13号染色体长臂上的癌基因并置而激活。 我们将通过评估t(813)淋巴瘤的FGFRI来回答这些假设 基因组重排和异常转录本。如果这些研究是 阴性，我们将继续筛选选定的表达的cdna文库 映射到8p易位断点区的序列。侯选人 癌基因将通过序列分析来鉴定，并将被用作 T(8；13)淋巴瘤细胞cDNA的Southern和Northern杂交探针 在Southern和/或Northern杂交上检测重排片段将是 作为锚定来识别13号染色体上相应的癌基因， 并将分离出这两个基因的全长cDNA。在生物学中的作用 将对t(8；13)癌蛋白进行生理学评估。 体外和体内的造血学和白血病 功能分析。

A novel variety of stem-cell leukemia/lymphoma involving T-cell, B-cell, and myeloid lineages has been described in the past three years. Most patients present with peripheral lymphadenopathy, and lymph node biopsies typically reveal T-cell lymphoblastic lymphoma. Concomitant bone marrow biopsy, on the other hand, generally demonstrates myeloid hyperplasia with pronounced eosinophilia. The lymphoma responds well to therapy, but most patients progress to a full-blown, rapidly fatal, acute myelogenous leukemia. It is notable that patients with this syndrome have balanced reciprocal translocation, involving chromosome bands 8p11 and 13q11-12, both in the lymphomatous peripheral nodes and in the myeloproliferative bone marrow cells. This observation suggests that translocation (8;13) is a critical oncogenetic event in a pluripotential cell capable of both myeloid and lymphoid differentiation. We have mapped the translocation (8;13) breakpoints using molecular cytogenetic approaches and have localized the 8p breakpoint to a 70 kb bacterial artificial chromosome (BAC) clone. Our preliminary BAC cDNA screening studies have implicated FGFRI as one candidate gene in the translocation (;13). We hypothesize that a gene at the translocation 8p breakpoint is oncogenic and is activated by juxtaposition with an oncogene on the chromosome 13 long arm. We will answer these hypotheses by evaluating t(813) lymphomas for FGFRI genomic rearrangements and aberrant transcripts. If those studies are negative, we will continue to screen selected cDNA libraries for expressed sequences mapping to the 8p translocation breakpoint region. Candidate oncogenes will be identified by sequence analysis and will be used as probes in Southern and Northern blots of t(8;13) lymphoma cells cDNAs detecting rearranged fragments on Southern and/or Northern blots will be used as anchors to identify the corresponding oncogene on chromosome 13, and full-length cDNAs will be isolated for both genes. Biologic role of the t(8;13) oncoproteins will be evaluated - both in physiologic hematopoiesis and in leukemogenesis - through in vitro and in vivo functional analysis.