Early gene activation in chronic leukemic B lymphocytes induced toward a plasma cell phenotype

作者: George B Segel , Timothy J Woodlock , Jia Xu , Liqiong Li , Raymond E Felgar

DOI: 10.1016/S1079-9796(03)00035-4

关键词: Pokeweed mitogenCD19Tetradecanoylphorbol AcetateBiologyImmediate early proteinGene expressionRegulation of gene expressionProtein phosphatase 2Molecular biologyCell activationMolecular medicineCell biologyHematology

摘要: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of lymphocytes that are arrested at an intermediate stage B lymphocyte development. CLL transform (mature) to a plasmacytic phenotype with loss CD19 and CD20 appearance cytoplasmic immunoglobulin when treated in vitro phorbol esters. We have used array hybridization technology describe gene expression patterns for untreated tetradecanoyl acetate (TPA)-treated cells 5, 10, 20 min following initial TPA exposure. Three genes, early growth response factor 1 (EGR-1), dual specificity phosphatase 2, CD69 (early T-cell activation antigen), showed 2.0-fold or greater increase mRNA transcription four more six time points two studies. Upregulation these genes was confirmed real-time polymerase chain reaction TPA-treated patients. A progressive observed during 20-min course all three genes. In addition, protein EGR-1 increased as measured immunofluorescence cell analysis. Several (PKC, n-myc, jun D, BCL-2) previously reported overexpressed were studies also, but not altered treatment. Genes proteins whose upregulation requires hours exposure (the 4F2hc component L-system amino acid transporter, prohibition, hsp60) assessed, their later contrasted EGR-1, CD69. encodes zinc-finger induced pokeweed mitogen promotes maturation. The 2 enzyme reverses activated kinase dephosphorylation. thymocytes type II transmembrane signaling molecule hematopoietic cells. These findings suggest products may be central steps TPA-induced evolution phenotype.

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