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Igβ(CD79b) mRNA expression in chronic lymphocytic leukaemia cells correlates with immunoglobulin heavy chain gene mutational status but does not serve as an independent predictor of clinical severity
Author(s) -
Cajiao Isabela,
Sargent Rachel,
Elstrom Rebecca,
Cooke Nancy E.,
Bagg Adam,
Liebhaber Stephen A.
Publication year - 2007
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.20885
Subject(s) - chronic lymphocytic leukemia , biology , ighv@ , somatic hypermutation , cd38 , immunology , messenger rna , antibody , gene expression , gene , breakpoint cluster region , immunoglobulin heavy chain , microbiology and biotechnology , b cell , genetics , leukemia , stem cell , cd34
The etiology of chronic lymphocytic leukemia (CLL) is poorly understood and its course is highly variable. Somatic hypermutation (SHM) of the immunoglobulin heavy chain ( IgV H ) gene and ZAP70 protein expression have been reported as prognostic indicators. However, these assays are not widely available and their concordance is imperfect. Thus a need exists to identify additional molecular determinants of CLL. The Igβ (CD79b) subunit of the B cell antigen receptor is essential for B lymphocyte function. Defects in Igβ expression are implicated in CLL pathogenesis. We have analyzed Igβ mRNA expression in CLL cells in 40 consecutive patient samples. About 75% of the samples showed the expected decrease of Igβ surface staining. Igβ mRNA levels covered a wider range, did not correlate with Igβ surface staining, but clearly distinguished the normal and CLL lymphocyte populations. Remarkably, Igβ mRNA levels correlated strongly with SHM; Igβ mRNA levels in CLL cells were significantly higher in patients with an unmutated IgV H gene when compared with those in whom IgV H was hypermutated (P = 0.008). In contrast, no correlation was observed between Igβ mRNA levels and ZAP70 expression. Multiple parameters abstracted from chart reviews were used to estimate severity of CLL in each case. While severity correlated strongly with ZAP70 staining, and to a lesser extent with SHM status, there was no correlation with Igβ mRNA levels. These data establish a strong linkage between Igβ mRNA expression and SHM in CLL and highlight the complex relationships between biochemical parameters and clinical status in this disease. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.