The Journal of Experimental Medicine
StemCell Technologies
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Published 2 June 2003. doi:10.1084/jem.20021726
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© Rockefeller University Press, 0022-1007/2003/6/1477 $5.00
The Journal of Experimental Medicine, Volume 197, Number 11, 1477-1488

Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma

Laszlo Kari1, Andrey Loboda1, Michael Nebozhyn1, Alain H. Rook2, Eric C. Vonderheid3, Calen Nichols1, Dezso Virok1, Celia Chang1, Wen-Hwai Horng1, James Johnston1, Maria Wysocka2, Michael K. Showe1 and Louise C. Showe1

1 Molecular Oncology Program, The Wistar Institute, Philadelphia, PA 19104
2 Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104
3 Department of Dermatology, The Johns Hopkins University, Baltimore, MD 21218

Address correspondence to Louise C. Showe, The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104. Phone: 215-898-3901; Fax: 215-898-3868; E-mail: lshowe{at}wistar.upenn.edu

We have used cDNA arrays to investigate gene expression patterns in peripheral blood mononuclear cells from patients with leukemic forms of cutaneous T cell lymphoma, primarily Sezary syndrome (SS). When expression data for patients with high blood tumor burden (Sezary cells >60% of the lymphocytes) and healthy controls are compared by Student's t test, at P < 0.01, we find 385 genes to be differentially expressed. Highly overexpressed genes include Th2 cells–specific transcription factors Gata-3 and Jun B, as well as integrin ß1, proteoglycan 2, the RhoB oncogene, and dual specificity phosphatase 1. Highly underexpressed genes include CD26, Stat-4, and the IL-1 receptors. Message for plastin-T, not normally expressed in lymphoid tissue, is detected only in patient samples and may provide a new marker for diagnosis. Using penalized discriminant analysis, we have identified a panel of eight genes that can distinguish SS in patients with as few as 5% circulating tumor cells. This suggests that, even in early disease, Sezary cells produce chemokines and cytokines that induce an expression profile in the peripheral blood distinctive to SS. Finally, we show that using 10 genes, we can identify a class of patients who will succumb within six months of sampling regardless of their tumor burden.

Key Words: cDNA microarrays • discriminant analysis • class prediction • prognosis • CTCL


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