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Forschungsdatenbank PMU-SQQUID

Difference in the relative distribution of CD4+ T-cell subsets in B-CLL with mutated and unmutated immunoglobulin (Ig) VH genes: implication for the course of disease.
Tinhofer, I; Weiss, L; Gassner, F; Rubenzer, G; Holler, C; Greil, R;
J Immunother. 2009; 32(3):302-309
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Brachtl Gabriele
Gassner Franz Josef
Greil Richard
Weiss Lukas

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is a clinically heterogeneous disease in which the clinical course is influenced by the presence or absence of immunoglobulin (Ig) variable heavy chain (VH) gene mutations. The poor clinical outcome of the subgroup with unmutated Ig VH genes has been linked to the persistent ability of the B-cell receptor in tumor cells from these cases to respond to antigen. As B-cell receptor signaling generally relies on T-cell help, we hypothesized that the course of B-CLL might not only be influenced by the Ig VH mutational status but also by the activation/differentiation status of T cells. We assessed the relative distribution of naive and memory T-cell subsets in peripheral blood from patients with mutated (M-CLL, n=71) and unmutated Ig VH genes (UM-CLL, n=42) and correlated it with the course of disease. We also compared the prosurvival potential of naive and memory T cells cocultured with B-CLL cells in vitro. A significant increase in relative numbers of central and effector memory T cells was observed in the CD4 T-cell pool from UM-CLL as compared with M-CLL cases and was associated with high Rai stage, progressive disease and shorter treatment-free survival (TFS). In a multivariate analysis, the relative number of CD4 central and effector memory T cells remained a significant prognostic parameter for TFS after correction for CD38 expression, Ig VH status, genomic aberrations, and Rai stage. The inverse correlation of memory CD4 T cells with TFS might be explained by their potential to support survival of B-CLL cells.


Useful keywords (using NLM MeSH Indexing)

Adult

Aged

Aged, 80 and over

B-Lymphocytes/immunology

B-Lymphocytes/metabolism

CD4-Positive T-Lymphocytes/immunology*

Coculture Techniques

DNA Mutational Analysis

Female

Humans

Immunoglobulin Heavy Chains/genetics*

Immunoglobulin Heavy Chains/immunology

Kaplan-Meier Estimate

Leukemia, Lymphocytic, Chronic, B-Cell/genetics

Leukemia, Lymphocytic, Chronic, B-Cell/immunology*

Leukemia, Lymphocytic, Chronic, B-Cell/mortality

Male

Middle Aged

Multivariate Analysis

Mutation

Regression Analysis

T-Lymphocyte Subsets/immunology*

T-Lymphocyte Subsets/metabolism


Find related publications in this database (Keywords)

leukemia
microenvironment
prognostic factor
CD4(+) T-cell subsets