[Effect of nuclear transcription factor RelB on the proteasome inhibitor-sensitivity of chronic lymphocytic leukemia...

To investigate the effect of nuclear transcription factor RelB on the proteasome inhibitor-sensitivity of chronic lymphocytic leukemia (CLL) cells.

The mRNA expression of RelB in CD5⁺ CD19⁺ CLL cells from BM was analyzed by reverse transcription PCR (RT-PCR). The RelB activity was examined by electromobility shift assay (EMSA) and an ELISA-based NF-κB family transcription factor activity assay. CLL cells were classified into RelB+ and RelB- groups according to RelB activity. The frequencies of cell death of CLL cells cultured with human bone marrow stromal cells (hBMSCs) after treatment with PS-341, MG-132 or fludarabine were determined by PI staining.

RelB mRNA expression and RelB activity could be detected in CLL cells at variable levels. Fludarabine (10 μmol/L), MG-132 (1 μmol/L) and PS-341 (1 μmol/L) could induce cell death of RelB+ and RelB- CLL cells co-cultured with hBMSCs in a time dependent manner. There was no significant difference in the fludarabine sensitivity between RelB+ and RelB- CLL cells, and the frequencies of cell death of RelB+ and RelB- CLL cells were (61.11 ± 6.91)% and (67.57 ± 9.45)%, respectively, when treated with fludarabine for 72 h. RelB+ CLL cells were more sensitive to MG-132 than RelB- CLL cells for 72 h, and the frequencies of cell death were (66.22 ± 3.39)% and (51.07 ± 5.93)%, respectively. RelB+ CLL cells were more sensitive to PS-341 than RelB- CLL cells for 24 and 48 h treatment, and the frequencies of cell death of RelB+ and RelB- CLL cells were (75.50 ± 4.66)% and (66.32 ± 10.20)% for 24 h, (92.11 ± 3.14)% and (85.84 ± 5.81)% for 48 h treatment, respectively.

The alternative NF-κB activity was detected in bone marrow derived CLL cells. Enhancement of RelB activity may increase CLL cells' sensitivity to proteasome inhibitor bortezomib and MG-132. However, the sensitivity of CLL cells to fludarabine had no relationship to RelB activity.