Classification and prediction of survival in patients with the leukemic phase of cutaneous T cell lymphoma.
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 beta1, 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.
Kari
Laszlo
L
Molecular Oncology Program, The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA.
Loboda
Andrey
A
Nebozhyn
Michael
M
Rook
Alain H
AH
Vonderheid
Eric C
EC
Nichols
Calen
C
Virok
Dezso
D
Chang
Celia
C
Horng
Wen-Hwai
WH
Johnston
James
J
Wysocka
Maria
M
Showe
Michael K
MK
Showe
Louise C
LC
D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D002454:Cell Differentiation; D016002:Discriminant Analysis; D020869:Gene Expression Profiling; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000145:classification* / Q000235:genetics / Q000401:mortality; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012751:Sezary Syndrome / Q000145:classification / Q000235:genetics / Q000401:mortality; D015996:Survival Rate; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology