Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors.

Abstract

BACKGROUND:

Numerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with "stereotyped" B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level.

DESIGN AND METHODS:

We investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays.

RESULTS:

Although generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients.

CONCLUSIONS:

Our novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.

• Authors: Millaray Marincevic, Mahmoud Mansouri, Meena Kanduri, Anders Isaksson, Hanna Göransson, Karin Ekström Smedby, Jesper Jurlander, Gunnar Juliusson, Fred Davi, Kostas Stamatopoulos, Richard Rosenquist
• Journal: Haematologica (Haematologica) Vol. 95 Issue 12 Pg. 2072-9 (Dec 2010) ISSN: 1592-8721 [Electronic] Italy
• PMID: 20801898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region
• Receptors, Antigen, B-Cell

Topics

• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Cluster Analysis
• Female
• Gene Rearrangement, B-Lymphocyte, Heavy Chain
• Humans
• Immunoglobulin Heavy Chains (genetics)
• Immunoglobulin Variable Region (genetics)
• Leukemia, Lymphocytic, Chronic, B-Cell (classification, genetics)
• Male
• Middle Aged
• Molecular Sequence Data
• Oligonucleotide Array Sequence Analysis
• Receptors, Antigen, B-Cell (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcriptome