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

Abstract

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 Igbeta (CD79b) subunit of the B cell antigen receptor is essential for B lymphocyte function. Defects in Igbeta expression are implicated in CLL pathogenesis. We have analyzed Igbeta mRNA expression in CLL cells in 40 consecutive patient samples. About 75% of the samples showed the expected decrease of Igbeta surface staining. Igbeta mRNA levels covered a wider range, did not correlate with Igbeta surface staining, but clearly distinguished the normal and CLL lymphocyte populations. Remarkably, Igbeta mRNA levels correlated strongly with SHM; Igbeta 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 Igbeta 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 Igbeta mRNA levels. These data establish a strong linkage between Igbeta mRNA expression and SHM in CLL and highlight the complex relationships between biochemical parameters and clinical status in this disease.