High Expression of Lymphocyte-Activation Gene 3 (LAG3) in Chronic Lymphocytic Leukemia Cells Is Associated with Unmutated Immunoglobulin Variable Heavy Chain Region (IGHV) Gene and Reduced Treatment-Free Survival
| Autor: | Jitka Kabáthová, Jana Kotašková, Jitka Malčíková, Michael Doubek, Jiri Mayer, Boris Tichy, Šárka Pospíšilová, Hana Skuhrová Francová, Martin Trbušek, Yvona Brychtová |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Chronic lymphocytic leukemia Genes Immunoglobulin Heavy Chain Immunoglobulin Variable Region Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine immune system diseases Antigens CD hemic and lymphatic diseases Gene expression medicine Humans 030304 developmental biology Aged Oligonucleotide Array Sequence Analysis Aged 80 and over 0303 health sciences ZAP-70 Protein-Tyrosine Kinase biology Microarray analysis techniques Reverse Transcriptase Polymerase Chain Reaction Middle Aged medicine.disease Leukemia Lymphocytic Chronic B-Cell Lymphocyte Activation Gene 3 Protein 3. Good health Reverse transcription polymerase chain reaction Survival Rate Leukemia Lipoprotein Lipase 030220 oncology & carcinogenesis Monoclonal Immunology Mutation biology.protein Cancer research Molecular Medicine Female Antibody IGHV@ Regular Articles |
| Popis: | Chronic lymphocytic leukemia (CLL) is characterized by a monoclonal expansion of mature B-lymphocytes. Mutational status of the immunoglobulin variable heavy chain region (IGHV) gene stratifies CLL patients into two prognostic groups. We performed microarray analysis of CLL cells using the Agilent platform to detect the most important gene expression differences regarding IGHV status in CLL cells. We analyzed a cohort of 118 CLL patients with different IGHV mutational status and completely characterized all described prognostic markers using expression microarrays and quantitative real-time RT-PCR (reverse transcription PCR). We detected lymphocyte-activation gene 3 (LAG3) as a novel prognostic marker: LAG3 high expression in CLL cells correlates with unmutated IGHV (P < 0.0001) and reduced treatment-free survival (P = 0.0087). Furthermore, quantitative real-time RT-PCR analysis identified a gene-set (LAG3, LPL, ZAP70) whose overexpression is assigned to unmutated IGHV with 90% specificity (P < 0.0001). Moreover, high expression of tested gene-set and unmutated IGHV equally correlated with reduced treatment-free survival (P = 7.7 * 10−11 vs. P = 1.8 * 10−11). Our results suggest that IGHV status can be precisely assessed using the expression analysis of LAG3, LPL, and ZAP70 genes. Expression data of tested markers provides a similar statistical concordance with treatment-free survival as that of the IGHV status itself. Our findings contribute to the elucidation of CLL pathogenesis and provide novel prognostic markers for possible application in routine diagnostics. |
| Databáze: | OpenAIRE |
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