Sezary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3
Sezary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3
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DOI：
10.1038/sj.leu.2405044
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发表时间：
2008-02-01
期刊：
影响因子：
11.4
通讯作者：
Goerdt, S.
中科院分区：
文献类型：
--
作者：
Booken, N.;Gratchev, A.;Goerdt, S.
Sezary综合征（SS）是一种罕见的侵袭性CD 4（+）皮肤T细胞淋巴瘤（CTCL）;将SS与非白血病性蕈样肉芽肿（MF）和炎性皮肤病（ID）区分开来的分子特征尚不充分。应用AffyphineU133Plus2.0芯片对10例SS患者和10例健康献血员（HD）外周血单个核细胞（PBMC）进行差异基因表达检测。通过qRT-PCR证实10个候选基因在SS与HD/ID的CD 4（+）T细胞中显著过表达。为了便于临床使用，这些基因在PBMC中重新分析; qRT-PCR证实5个新基因（DNM 3、IGFL 2、CDO 1、NEDD 4L、KLHDC 5）和2个已知基因（PLS 3、TNFSF 11）在SS中显著过表达。多因素Logistic回归分析显示，CDO 1和DNM 3联合使用的鉴别力最高。在比较SS与MF的PBMC和皮肤样品时，发现CDO 1和DNM 3仅在SS中上调。使用抗-CDO 1抗血清，证实在SS CD 4（+）T细胞中CDO 1蛋白的差异表达。有趣的是，已知DNM 3和CDO 1分别受SS相关转录因子TWIST 1和c-myb调控。此外，CDO 1催化牛磺酸合成，牛磺酸抑制细胞凋亡并促进化学保护。总之，CDO 1和DNM 3可以提高SS的诊断，并为其发病机制提供新的线索。
Sezary syndrome (SS) is a rare, aggressive CD4(+) cutaneous T-cell lymphoma (CTCL); molecular traits differentiating SS from nonleukemic mycosis fungoides (MF) and from inflammatory skin diseases (ID) are not sufficiently characterized. Peripheral blood mononuclear cells (PBMC) of 10 SS patients and 10 healthy donors (HD) were screened by Affymetrix U133Plus2.0 chips for differential gene expression. Ten candidate genes were confirmed by qRT-PCR to be significantly overexpressed in CD4(+) T cells of SS versus HD/ ID. For easier clinical use, these genes were re-analyzed in PBMC; qRT-PCR confirmed five novel (DNM3, IGFL2, CDO1, NEDD4L, KLHDC5) and two known genes (PLS3, TNFSF11) to be significantly overexpressed in SS. Multiple logistic regression analysis revealed that CDO1 and DNM3 had the highest discriminative power in combination. Upon comparison of PBMC and skin samples of SS versus MF, CDO1 and DNM3 were found upregulated only in SS. Using anti-CDO1 antisera, differential expression of CDO1 protein was confirmed in SS CD4(+) T cells. Interestingly, DNM3 and CDO1 are known to be regulated by SS-associated transcription factors TWIST1 and c-myb, respectively. Furthermore, CDO1 catalyzes taurine synthesis and taurine inhibits apoptosis and promotes chemoprotection. In summary, CDO1 and DNM3 may improve the diagnosis of SS and open novel clues to its pathogenesis.