Gene expression profiling of cell lines derived from T‐cell malignancies

Abstract

The expression pro¢les of eight cell lines derived from T-cell malignancies were compared to CD4-positive T-cells using cDNA microarray technology. Unsupervised hierarchical clustering of 4364 genes demonstrated substantial heterogeneity resulting in four distinct groups. While no genes were found to be uniformly up-or down-regulated across all cell lines, we observed 111 over-expressed genes (greater than two-fold) and 1118 down-regulated genes (greater than two-fold) in the lymphomas as a group when compared to CD4-positive T-cells. These included genes involved in cytokine signaling, cell adhesion, cytoskeletal elements, nuclear transcription factors, and known oncogenes and tumor suppressor genes. Quantitative £uorescent reverse transcription-polymerase chain reaction analysis demonstrated 70% concordance with the microarray results. While freshly isolated malignant cells may di¡er in their individual expression patterns relative to established cell lines from the same diagnoses, we feel that the variety of di¡erent lymphocytic cell lines that we examined provides a representative picture of the molecular pathogenesis of T-cell malignancies. ß

Expression Profiling of T-Cell Lymphomas Differentiates Peripheral and Lymphoblastic Lymphomas and Defines Survival Related Genes

“…We maintain that much fewer genes, compared with those that differentiate peripheral T-cell lymphoma and lymphoblastic T-cell lymphomas, might be distinguishing among the different subtypes of periph- eral T-cell lymphoma. Using different T-cell lines, significant heterogeneity in the expression profiles has been previously reported, although not with a complete correlation to the clinicopathologically related categories (14). In contrast, the comparison of peripheral T-cell lymphoma with normal samples revealed a subset of 17 and 35 significantly differentially expressed genes between all peripheral T-cell lymphoma tumors and normal T lymphocytes or reactive lymph nodes, respectively (see Fig.…”

“…A supervised method was then used to find the more significant (adjusted P Ͻ 0.05) differentially expressed genes among peripheral T-cell lymphomas and lymphoblastic T-cell lymphomas (see supplementary data online). 14 We found 184 clones representing 160 genes that were differentially expressed between these two classes (Fig. 2).…”

“…The genes obtained being associated to these variables can be found in the supplementary material. 14 We performed correlation analysis among genes more related to survival and those genes associated to stage of disease, proliferation index, and response to treatments (Fig. 6).…”

Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes

“…32-35 T-cell lymphomas represent a heterogeneous group of tumors that could benefit from DNA microarrays for defining unrecognized subcategories, identifying new oncogenic pathways or pathogenetically relevant genes and biologic predictors for their clinical course. With the exception of previous reports based on cell lines derived from T-cell malignancies, [36][37][38] few studies involve biopsy specimens from patients with T-cell lymphomas. [32][33][34][35] In the study by Martinez-Delgado et al, 32 gene-expression profiles have been analyzed in 34 peripheral T-cell lymphoma pertaining to different categories.…”

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.…”