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 Igb (CD79b) subunit of the B cell antigen receptor is essential for B lymphocyte function. Defects in Igb expression are implicated in CLL pathogenesis. We have analyzed Igb mRNA expression in CLL cells in 40 consecutive patient samples. About 75% of the samples showed the expected decrease of Igb surface staining. Igb mRNA levels covered a wider range, did not correlate with Igb surface staining, but clearly distinguished the normal and CLL lymphocyte populations. Remarkably, Igb mRNA levels correlated strongly with SHM; Igb 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 5 0.008). In contrast, no correlation was observed between Igb 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 Igb mRNA levels. These data establish a strong linkage between Igb mRNA expression and SHM in CLL and highlight the complex relationships between biochemical parameters and clinical status in this disease. Am. J. Hematol. 82:712-720, 2007. V

Role of long non-coding RNAs in disease progression of early stage unmutated chronic lymphocytic leukemia

“…By RT-qPCR we were able to demonstrate that the associated mRNAs RALA and RAD51B were similarly differentially expressed, despite the lack of differential expression in the original mRNA microarray data (Figure 8B). The lncRNAs T204050 (FC=3.6), NR_002947 (FC=8.3), and uc.436+ (FC=2.8) have known or nearby protein coding genes implicated in CLL biology [52–54]. RT-qPCR expression patterns of all 3 of these lncRNAs were consistent with the microarray data.…”

“…Biologically relevant in CLL, the lncRNA NR_002947 and mRNA for its associated protein CD79b were found to be differentially expressed by both microarray and RT-qPCR and displayed opposite expression levels suggesting that CD79b expression may be altered by NR_002947. CD79b is a critical component of the B cell receptor and levels of CD79b mRNA have been shown to be higher in UM CLL even though surface expression of CD79b remains low [52]. However, Guo et al have shown that IL-4 restores CD79b protein expression at the post-transcriptional level and speculated that aberrant expression of micro-RNAs may be playing a role [64].…”

The phosphoinositide 3-kinase signaling pathway in normal and malignant B cells: activation mechanisms, regulation and impact on cellular functions

“…Compared to normal B cells, B-CLL exhibit low surface expression of Ig and CD79b, associated with low levels of mRNA encoding for CD79b (Thompson et al, 1997). CD79b mRNA level was however found to be higher in the more severe CLL prognostic group associated with unmutated Ig heavy chain variable (V H ) genes (Cajiao et al, 2007), suggesting a possible link between CD79b expression and disease severity. Some authors have compared this BCR-low phenotype to “anergic” B cells which, in animal models, down-modulate surface BCR in response to chronic BCR stimulation by low affinity or soluble self-Ags.…”