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Surface antigen expression and correlation with variable heavy-chain gene mutation status in chronic lymphocytic
Juhani Vilpo1, Gerard Tobin, Janne Hulkkonen
1Department of Clinical Chemistry, University of Tampere Medical School, Laboratory Center of Tampere University Hospital, Tampere, Finland.
European Journal of Haematology
|March 13, 2003
Summary
Chronic lymphocytic leukemia (CLL) has two subtypes: mutated (M-CLL) and unmutated (UM-CLL) immunoglobulin heavy chain genes. This study reveals largely similar surface antigen expression between M-CLL and UM-CLL, with notable differences in CD45 isoforms.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- B-cell chronic lymphocytic leukemia (CLL) is classified into two clinical entities based on immunoglobulin heavy-chain variable (VH) gene mutation status: mutated (M-CLL) and unmutated (UM-CLL).
- The cellular biology and surface antigen expression of these distinct CLL subsets remain largely unexplored.
Purpose of the Study:
- To extensively analyze surface antigen expression in CLL patients.
- To correlate surface antigen expression patterns with VH gene mutation status in M-CLL and UM-CLL.
- To investigate the cellular phenotype of M-CLL and UM-CLL subsets.
Main Methods:
- Analysis of 32 CLL patients' peripheral blood leukemic cells.
- Polymerase chain reaction amplification and nucleotide sequencing to determine VH gene mutation status.
- Flow cytometry analysis of 27 surface membrane antigens, measuring positive cell percentage and geometric mean fluorescence intensity (GMF).
Main Results:
- VH genes were mutated in 31% (M-CLL) and unmutated in 69% (UM-CLL) of cases.
- Most surface antigens (e.g., CD5, CD19, CD20, CD23) showed similar expression patterns in both M-CLL and UM-CLL, indicating a homogeneous phenotype.
- CD45RO expression was significantly associated with M-CLL, while CD45RA intensity tended to be associated with UM-CLL. Ig-lambda+ was more frequent in M-CLL (70%) than UM-CLL (36%).
Conclusions:
- M-CLL and UM-CLL exhibit a considerably homogeneous phenotype regarding most surface antigens, challenging previous assumptions of distinct cellular biology.
- CD27 expression in all cases suggests a memory cell phenotype for both CLL subsets.
- Differential expression of CD45 isoforms (CD45RO and CD45RA) highlights potential distinct roles in CLL pathogenesis requiring further investigation.