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 β1, 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.
Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma
L. Kari, A. Loboda, and M. Nebozhyn contributed equally to this work.
The online version of this article includes supplemental material.
Abbreviations used in this paper: CTCL, cutaneous T cell lymphoma; DUSP1, dual specificity phosphatase 1; FP, false positives; IL-1R, IL-1 receptor; LT, long-term; MF, mycosis fungoides; MT, intermediate; PDA, penalized discriminant analysis; PLS3, plastin T; QPCR, quantitative PCR; SG, significant genes; SS, Sezary syndrome; ST, short-term; STAT4, signal transducer and activator of transcription 4.
Laszlo Kari, Andrey Loboda, Michael Nebozhyn, Alain H. Rook, Eric C. Vonderheid, Calen Nichols, Dezso Virok, Celia Chang, Wen-Hwai Horng, James Johnston, Maria Wysocka, Michael K. Showe, Louise C. Showe; Classification and Prediction of Survival in Patients with the Leukemic Phase of Cutaneous T Cell Lymphoma . J Exp Med 2 June 2003; 197 (11): 1477–1488. doi: https://doi.org/10.1084/jem.20021726
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