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

The usage of the immunoglobulin (19) 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 (similar to 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 efflicient 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.