Silencing of PTPN22 in primary CLL cells enhances proapoptotic and inhibits antiapoptotic BCR signals. (A) CLL cells were transfected with control (siCTRL) or PTPN22 (siPTP) siRNA and placed in culture with bone marrow stromal cells to inhibit spontaneous and nucleofection-induced apoptosis. After 48 hours, CLL cells were removed from the layer of stromal cells and were cultured for additional 48 hours without (unstim.) or with soluble or immobilized anti-IgM (sol-aIgM and imm-aIgM, respectively). The percentage of viable cells was determined by annexin V/PI staining and flow cytometry. One representative experiment of 11 is shown. Viable cells bound with beads coated with imm-aIgM are seen as a separate population. PTPN22 protein levels in the same sample are shown in the bottom panel. Normal B cells (TB9) were used as a standard to evaluate the efficiency of PTPN22 down-regulation. (B) Summary of the data obtained with 11 different CLL samples. Significance of differences in leukemic cell viability was evaluated with the paired t test.