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Molecular profiling of LGL leukemia reveals role of sphingolipid signaling of cytotoxic lymphocytes

ABSTRACT: We used microarrays to expression profile peripheral blood mononuclear cells (PBMCs) from LGL leukemia patients and control subjects to identify survival pathways that render leukemic LGL resistant to activation induced cell death. Keywords: granular lymphocyte leukemia, PBMC

ORGANISM(S): Homo sapiens

PROVIDER: GSE10631 | GEO | 2008/05/01

SECONDARY ACCESSION(S): PRJNA107699

REPOSITORIES: GEO

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Transcription profiling of human peripheral blood mononuclear cells isolated from LGL leukemia samples reveals role of sphingolipid signaling of cytotoxic lymphocytes

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Project description:Recent studies suggest the potential involvement of common antigenic stimuli on the ontogeny of monoclonal TCRalphabeta+/CD4+/NKa+/CD8-/+dim T-large granular lymphocyte (LGL) lymphocytosis. Since healthy individuals show (oligo)clonal expansions of hCMV-specific TCRVbeta+/CD4+/cytotoxic/memory T-cells, we investigate the potential involvement of hCMV in the origin and/or expansion of monoclonal CD4+ T-LGL. A detailed characterization of those genes that underwent changes in T-LGL cells responding to hCMV was performed by microarray gene expression profile (GEP) analysis. Experiment Overall Design: Total RNA was isolated from magnetic-activated cell sorter (MACS)-freshly purified hCMV-stimulated CD69+, hCMV-stimulated CD69- and unstimulated monoclonal CD4+ T-LGL lymphocytes from PB samples from four TCRVbeta+/CD4+ T-LGL lymphocytosis patients (purity of â?¥98%). Briefly, 100 ng of total RNA from each of the 12 purified cell fractions was amplified and labeled using the GeneChip two cycle cDNA synthesis kit and the GeneChip IVT labeling kit (Affymetrix Inc., Santa Clara, CA), respectively. Then it was hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix). Experiment Overall Design: In parallel, total RNA was also isolated from highly purified (â?¥ 98% purity) hCMV-stimulated (specific) CD69+ CD4+ T-lymphocytes isolated from PB samples from hCMV-seropositive healthy donors (n=5, mean age of 36 years) using a FACSAria flow cytometer (BDB). To get pure and highly concentrated RNA, the silica membrane technology NucleoSpinÂ® RNA XS (Macherey-Nagel, DÃ¼ren, Germany) was used. Total RNA was then amplified, labeled and hybridized to the Human Genome U133 Plus 2.0 Array (Affymetrix) as described above.

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Project description:Genomic Architecture of LGL leukemia

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