MOLECULAR CHARACTERIZATION OF CUTANEOUS T-CELL LYMPHOMA

描述（改编自申请人摘要）：皮肤T细胞 淋巴瘤（CTCL）构成T淋巴细胞的恶性增殖， 最初累及皮肤，但后来发展为累及淋巴结， 血液和其他内脏器官。 早期皮肤病的诊断 以及隐匿性皮肤外受累仍然很困难， 当前诊断的灵敏度和特异性的局限性 技术. 最近，研究人员成功地从分子水平上 通过克隆T细胞抗原受体β链（TCR-B）诊断CTCL 恶性T细胞的基因重排，并产生患者特异性 寡核苷酸探针能够检测这种疾病， 聚合酶链反应（PCR）扩增。 调查人员打算 利用这项技术： (1)检测微小残留病的存在;（2）证明 皮肤中恶性克隆的最早存在;（3）确定 全身（皮外）受累的最早发作。 他们预计 这些实验的结果将阐明 CTCL在个体患者中，有助于了解其起源 和CTCL的进展，为分子诊断提供新的探针， 治疗监测和原位杂交。 而且他们 预计快速克隆TCR-B基因重排的能力将奠定 新的治疗方法的基础，旨在免疫调节 人类T细胞恶性肿瘤中的致病性T细胞克隆。

DESCRIPTION (Adapted from the applicant's abstract): Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferation of T-lymphocytes that initially involves the skin, but later progresses to involve lymph nodes, blood, and other visceral organs. Diagnosis of early cutaneous disease as well as occult extra-cutaneous involvement remains difficult due to the limitations of sensitivity and specificity of current diagnostic techniques. Recently the investigators have succeeded in molecularly diagnosing CTCL by cloning the T-cell antigen receptor beta chain (TCR-B) gene rearrangement from malignant T-cells and generating patient-specific oligonucleotide probes which are capable of detecting this disease through polymerase chain reaction (PCR) amplification. The investigators intend to utilize this technique to: (1) Detect the presence of minimal residual disease; (2) demonstrate the earliest presence of the malignant clone in the skin; (3) determine the earliest onset of systemic (extracutaneous) involvement. They anticipate that the results of these experiments will elucidate the natural history of CTCL in individual patients, contribute to an understanding of the origin and progression of CTCL, and provide new probes for molecular diagnosis, therapeutic monitoring, and in-situ hybridization. Furthermore, they expect that the ability to clone TCR-B gene rearrangements rapidly will lay the foundation for new therapeutic approaches aimed at the immunomodulation of pathogenic T-cell clones in human T-cell malignancies.