We found that use of either Oxamflatin (Oxam) or Trichostatin A (TSA), two hydroxamic acid-based HDACis, sensitized B-CLL cells to TRAIL-mediated apoptosis, due to their ability to upregulate both TRAIL-R1 and TRAIL-R2, increase activation of caspase 8, and increase expression of the proapoptotic protein Bax while decreasing expression of the antiapoptotic molecules Bcl-xL and Bcl-2. This evidence concerns the gene CASP8 and B-cell chronic lymphocytic leukemia.