Proteomic analysis of anaplastic lymphoma cell lines: Identification of potential tumour markers

Proteomic analysis of anaplastic lymphoma cell lines: Identification of potential tumour markers
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DOI:
10.1002/pmic.200500647
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发表时间:
2006-05-01
期刊:
影响因子:
3.4
通讯作者:
Payrastre, Bernard
Payrastre, Bernard
中科院分区:
生物学3区
文献类型:
--
作者:
Cussac, Daniel;Pichereaux, Carole;Payrastre, Bernard

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间变性大细胞淋巴瘤(ALCL)是Tor无效表型的高级别淋巴瘤,通常与t(2;5)易位相关。导致由核磷蛋白(NPM)的N末端部分和间变性淋巴瘤激酶(ALK)的细胞内结构域组成的嵌合蛋白的表达。尽管ALCL被认为是不同的临床、生物学和细胞遗传学实体,但在这组肿瘤中仍存在异质性,表现出广泛的形态学特征。特别地,由大细胞组成的普通型肿瘤与有时与白血病期相关的小细胞变体形成对比。ALK阴性ALCL通常与预后不良相关。在这里,我们使用患者来源的细胞系研究了这些肿瘤亚型的蛋白质组。我们一方面比较了NPM-ALK阳性与NPM-ALK阴性细胞胞质组分的蛋白质组,另一方面比较了常见细胞类型与小细胞变体的蛋白质组。在ALCL亚型中差异表达的一组蛋白质的鉴定指向新的诊断/预后标志物。本研究还提供了有关ALCL不同亚型的分子机制的有趣信息。
Anaplastic large-cell lymphomas (ALCL) are high grade lymphomas of Tor null phenotype often associated with the t(2;5) translocation. leading to the expression of a chimeric protein consisting of the N-terminal portion of nucleophosmin (NPM) and the intracellular domain of the anaplastic lymphoma kinase (ALK). Although ALCL are recognized as distinct clinical, biological and cytogenetic entities, heterogeneities persist in this group of tumours, which exhibit a broad spectrum of morphological features. Particularly, the common type tumour consisting in large cells contrast with the small cell variant that is sometimes associated with a leukemic phase. The ALK-negative ALCL is often associated with a poor prognosis. Here, we investigated the proteome of these subtypes of tumours using patient-derived cell lines. We compared the proteome of the cytosolic fraction of NPM-ALK-positive versus NPM-ALK-negative cells on one hand, and the proteome of common cell type versus small cell variant on the other hand. The identification of a set of proteins differentially expressed in the subtypes of ALCL points to new diagnosis/ prognosis markers. This study also provides interesting information on the molecular mechanisms responsible for the different subtypes of ALCL.