Comparison of Gene Expression between T Cells from CLL Patients, Myeloma Patients and Healthy Individuals.

Abstract

A unique feature of chronic lymphocytic leukemia is the expansion in absolute numbers of circulating T cells, accompanying the increase in the leukemic B cell clone. T cells of CLL patients may have a role in contributing to the microenvironment that favors the survival and progression of the malignant clone. We have looked at the gene profile of highly purified peripheral T cells from indolent CLL patients using Affymetrix global gene arrays and compared them with purified T cells from multiple myeloma patients as well as healthy individuals. T cells from five indolent, treatment-naïve CLL patients were examined for gene expression by Affymetrix-based microarray alongside T cells from 5 stage I, multiple myeloma patients and 5 age-matched healthy volunteers. Differential expression analysis revealed that 356 genes were differentially expressed by T cells from CLL patients. Based on a two-fold or greater difference, 107 genes were specifically upregulated and 247 genes were noted to be specifically downregulated in T cells of CLL patients. The highest level of upregulation was noted for the chemokines XCL1, XCL2, and the cytokine IFN-g. CCL4 and CCL5 were two other important chemokines that also were found to be specifically upregulated in T cells of B-CLL patients as well as KLF6 and TRAF1. The findings of the microarray analysis was further confirmed using quantitative real-time PCR and immunoblotting with specific antibodies. using T cells from an additional 14 CLL, 6 multiple myeloma and 10 healthy individuals. Our results indicate that T cells from B CLL patients may express a variety of genes that contribute to the creation of a microenvironment that sustains the survival of the leukemic clone and may produce soluble factors that inhibit apoptosis and facilitate proliferation of the leukemic B cells.