Altogether, these results showed that in the progressive U-CLL subgroup key genes of the TGF-β/SMAD pathway (SMAD-2, SMAD-4, p21−Cip1 and KLF10) are decreased, suggesting that the signaling provided for this axis could be inhibited in the CLL cells. Here, SMAD4 is linked to B-cell chronic lymphocytic leukemia.