Sezary syndrome is a unique cutaneous T-cell lymphoma as identified by an expanded gene signature including diagnostic marker molecules CDO1 and DNM3

被引:88
作者
Booken, N. [1 ]
Gratchev, A. [1 ]
Utikal, J. [1 ]
Weiss, C. [2 ]
Yu, X. [3 ]
Qadoumi, M. [1 ]
Schmuth, M. [4 ]
Sepp, N. [4 ]
Nashan, D. [5 ]
Rass, K. [6 ]
Tueting, T. [7 ]
Assaf, C. [8 ]
Dippel, E. [1 ,9 ]
Stadler, R. [10 ]
Klemke, C-D [1 ]
Goerdt, S. [1 ]
机构
[1] Heidelberg Univ, Univ Med Ctr Mannheim, Dept Dermatol Venerol & Allergol, D-68167 Mannheim, Germany
[2] Heidelberg Univ, Univ Med Ctr Mannheim, Inst Med Stat, D-68167 Mannheim, Germany
[3] Heidelberg Univ, Univ Med Ctr Mannheim, Med Res Ctr ZMF, D-68167 Mannheim, Germany
[4] Innsbruck Med Univ, Dept Dermatol, Innsbruck, Austria
[5] Univ Freiburg, Dept Dermatol, Freiburg, Germany
[6] Saarland Univ Hosp, Dept Dermatol, Homburg, Germany
[7] Univ Bonn, Dept Dermatol, D-5300 Bonn, Germany
[8] Charite, Dept Dermatol, D-13353 Berlin, Germany
[9] Acad Med Ctr, Dept Dermatol, Lemgo, Germany
[10] Acad Med Ctr, Dept Dermatol, Minden, Germany
关键词
Sezary syndrome; DNA arrays; cysteine dioxygenase; dynamin; 3; diagnostic markers;
D O I
10.1038/sj.leu.2405044
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:393 / 399
页数:7
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