PATHOGENESIS OF HUMAN T-CELL LEUKEMIAS/LYMPHOMAS

这项提议的目标是识别和表征可能的基因。 与T细胞白血病和淋巴瘤的发病机制有关 男性14号染色体q11.2-q32.2区域倒位/易位。 针对T细胞受体离子α链基因的cDNAs探针 14q11.2)用于Southern杂交克隆 14q11.1-q32.2易位/倒位涉及的断裂点。这个 14号染色体q32.2带上的原癌基因，我们建议 TCL-1(T细胞性白血病/淋巴瘤-1)的名称将通过“行走”来识别 上游到阿尔法链轨迹，如在对B细胞所做的类似工作中 携带涉及免疫球蛋白重度易位的恶性肿瘤 链式轨迹。在这样做的时候，我们将获得核酸探针来识别 并对TCL-1基因进行了表征，这是一种似乎是 与迄今所描述的任何已知的逆转录病毒癌基因无关。这个 TCL-1基因将被完全测序；能够 激活原癌基因将被定义。我们会研究 在正常T细胞和恶性T细胞中对其表达的调节 静止期和增殖期T细胞以及各种正常和 肿瘤组织。我们还将生产针对TCL-1基因的抗体 产品以确定其蜂窝位置并用于其 表征和提纯。 这项研究应该会更好地理解基因 导致T细胞肿瘤的机制，并应提供可使用的探针 在对这种人类恶性肿瘤的诊断中。

The goal of this proposal is to identify and characterize possible genes involved in the pathogenesis of T-cell leukemias and lymphomas with the inversion/translocation of the region q11.2-q32.2 of chromosome 14 in man. cDNA probes specific for the alpha-chain locus of the T-cell receptor ion 14q11.2) will be used in Southern blot hybridization to clone the breakpoint involved in the 14q11.1-q32.2 translocation/inversion. The proto-oncogene on band q32.2 of chromosome 14, for which we propose the name of tcl-1 (T-cell leukemia/lymphoma-1) will be identified by "walking" upstream to the alpha-chain locus, as in analogous work done with B-cell malignancies carrying translocations involving the immunoglobulin heavy chain locus. In doing so, we will obtain nucleic acid probes to identify and characterize the tcl-1 gene, a proto-oncogene which appears to be unrelated to any of the known retrovirus oncogenes described to date. The tcl-1 gene will be entirely sequenced; the genetic elements capable of activating the proto-oncogene will be defined. We will study the regulation of its expression in normal versus malignant T-cells, in quiescent versus proliferating T-cells and in a variety of normal and neoplastic tissues. We will also produce antibodies against the tcl-1 gene product to determine its cellular location and to be used for its characterization and purification. This study should result in a better understanding of the genetic mechanisms leading to T-cell neoplasia and should provide probes to be used in the diagnosis of this human malignancy.