Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B cell receptors
2010 (English)In: Haematologica (online), ISSN 0390-6078, E-ISSN 1592-8721, Vol. 95, no 12, 2072-2079 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2010. Vol. 95, no 12, 2072-2079 p.
Chronic lymphocytic leukemia, Gene expression, IGHV4-34, Stereotyped BCR
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-132891DOI: 10.3324/haematol.2010.028639ISI: 000285571400013PubMedID: 20801898OAI: oai:DiVA.org:uu-132891DiVA: diva2:359576