Based on this hypothesis, we can speculate that blockade of CTLA-4 on CLL cells as well as on normal B lymphocytes may lead to inactivation of PI3K-related pathways, resulting in decreased expression of cyclins D2 and D3, and accumulation of p27KIP1 protein, in consequence. This evidence concerns the gene CDKN1B and B-cell chronic lymphocytic leukemia.