Distinctive gene expression pattern in VH3-21 utilizing B-cell chronic lymphocytic leukemia

Abstract

The usage of the immunoglobulin (Ig) V(H)3-21 gene is associated with poor prognosis in B-cell chronic lymphocytic leukemia (B-CLL) despite V(H) gene mutation status. Many V(H)3-21+ patients also display restricted heavy- and light-chain Ig gene rearrangements, implying a role of antigen selection in disease development. To explore the specific phenotypic/genotypic features among V(H)3-21+ B-CLLs, we compared gene expression patterns in 15 V(H)3-21+ and 24 non-V(H)3-21 patients (11 with unmutated and 13 with mutated V(H) genes) using Affymetrix microarray analysis (approximately 12,500 genes). A distinct expression profile was identified for V(H)3-21+ patients in contrast to the Ig-unmutated and -mutated groups. By applying different algorithms, the data enabled an efficient class discrimination of the V(H)3-21+ subset based on 27 or 57 genes. A set of genes was sorted out which, using different analytical methods, consistently gave a distinction between V(H)3-21+ and non-V(H)3-21 samples. Several of these genes are involved in regulation of DNA replication/cell-cycle control, transcription and protein kinase activity, which may render the V(H)3-21+ cells with a higher proliferative drive. However, no clear evidence of increased B-cell receptor signaling was found in the V(H)3-21+ group. Altogether, our identification of a specific V(H)3-21 profile may provide insights into the pathogenesis of the V(H)3-21+ subgroup.