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

Abstract

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.

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

“…Of note, MF/SS is associated with the expression of Th2-associated genes (e.g., GATA-3) and the production of Th2-associated cytokines (e.g., IL-4, IL-5, and IL-10), thus raising the possibility that a significant subset of patients may harbor Th2-derived clones [32][33][34][35][36]. As the cell of origin is further defined in subsets of CTCL, including MF/SS, one may anticipate that this data may have a significant impact on the classification, risk-stratification, and treatment of these diseases.…”

“…Cyclin upregulation, including cyclinD1, and loss of RB1 have also been described [94]. As gene-expression profiling and nextgeneration sequencing technologies are used, additional pathogenic pathways, including those involving transcription factors regulating T-cell differentiation [35,36], c-MYC [95,96], RAS/RAF/MEK signaling [97], among others [90,98], may be identified in subsets of CTCL.…”

Elevated expression of protein biosynthesis genes in liver and muscle of hibernating black bears (Ursus americanus)

“…Samples of total RNA were linearly amplified with Illumina TotalPrep RNA Amplification Kit (Ambion), and 1.6 g of the amplified RNA was labeled with 65 Ci of [ 33 P]dCTP as previously described (20). All RNA samples were amplified, labeled, and hybridized in the same batch.…”

Gene expression profiling identifies molecular subgroups among nodal peripheral T-cell lymphomas

“…Analysis of several B-NHLs series has led to the definition of molecular subgroups with specific outcomes (Alizadeh et al, 2000;Rosenwald et al, 2002;Shipp et al, 2002;Thieblemont et al, 2004). In contrast, only a limited number of T-cell neoplasms have been investigated using microarrays, including mycosis fungoides (Tracey et al, 2003), leukemic phase of cutaneous T-NHL (Kari et al, 2003), cell lines derived from T-cell malignancies (Li et al, 2001;Fillmore et al, 2002), or PTCL (Martinez-Delgado et al, 2004). A recent profiling analysis was focused on the comparison between PTCL and T-lymphoblastic lymphoma (T-LBL) types (Martinez-Delgado et al, 2004), but a molecular classification of PTCL entities has not yet been reported.…”