Molecular Pathways of Interleukin-13 in Cutaneous T-cell Lymphoma

摘要 皮肤T细胞淋巴瘤(CTCL)是一组异质性的T淋巴细胞 主要影响皮肤的恶性肿瘤。真菌病是最常见的一种 CTCL的形式，通常运行一个懒惰的过程。然而，在相当数量的 患者病情可能会恶化，肿瘤细胞会扩散到身体其他部位 导致了致命的后果。诊断多发性骨髓瘤，特别是在早期阶段，很难。 由于缺乏恶性淋巴细胞的特异性标记物而建立。有限 晚期MF患者可选择治疗方案，这反映了 对疾病发病机制认识不足。 我们最近证明了IL-13及其受体代表着新的肿瘤标志物。 恶性多发性骨髓瘤。我们的研究进一步证实了IL-13通过信号转导途径 转录转导和激活因子-6(STAT-6)蛋白。值得注意的是，我们发现 MF患者皮肤中大量激活的STAT-6+细胞，尤其是 在高级阶段。在这里，我们建议分析IL-13的分子途径 侵袭型多发性骨髓瘤对恶性细胞的信号传导。我们的中心假设是 STAT-6是MF发病机制中的一个主要因素，在促进 疾病的发展，是潜在的治疗目标。具体的 这项建议的目标是牢固地基于我们以前的结果，并专注于确定 STAT-6在MF发病机制中的独特作用 IL-13诱导MF肿瘤细胞增殖的分子机制。 确定MF的发病机制将揭示新的诊断试剂和 分子靶点，导致针对这种疾病的创新疗法。

Abstract Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of T lymphocytes malignancies that primarily affect skin. Mycosis fungoides (MF) is the most common form of CTCL and typically runs an indolent course. However, in a significant number of patients the disease may progress and tumor cells spread to other sites of the body leading to a fatal outcome. Diagnosis of MF, especially in the early stages, is difficult to establish due to the absence of specific markers for malignant lymphocytes. Limited treatment options are available for patients with advanced-stage MF, a reflection of the poor understanding of disease pathogenesis. We have recently demonstrated that IL-13 and its receptors represent novel markers of malignancy in MF. Our studies further implicated IL-13 signaling via the Signal Transducer and Activator of Transcription-6 (STAT-6) protein. Significantly, we found high numbers of activated STAT-6+ cells in the affected skin of MF patients, particularly in advanced stages. Here we propose to analyze the molecular pathways of IL-13 signaling in malignant cells from aggressive forms of MF. Our central hypothesis is that STAT-6 is a major factor in the pathogenesis of MF that is critical in promoting disease progression and represents a potential target for therapy. The Specific Aims of this proposal are based solidly on our previous results and focus on identifying the unique role of STAT-6 in the pathogenesis of MF, thus shedding light on the molecular mechanisms underlying IL-13-induced tumor cell proliferation in MF. Identifying the mechanisms of MF pathogenesis will reveal novel diagnostic agents and molecular targets, leading to innovative therapies against this disease.