AP2 Overexpression: Correlation to a Poor Prognosis in CLL.

Inhibitors of apoptosis proteins (IAPs) are a group of structurally related proteins that block apoptosis either by binding and inhibiting caspases or through caspases-independent mechanisms. Overexpression of IAPs has been detected in several types of cancers, including hematological malignancies, and it is correlated with chemotherapeutic resistance. B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of mature lymphocytes due to defective apoptosis. During disease progression, many patients acquire resistance to chemotherapeutic drugs, perhaps attributable, in large part, to the defects in programmed cell death. To verify whether IAPs expression could be responsible for chemotherapeutic resistance or disease progression we analyzed, by immunocitochemistry, the expression of c-IAP1, c-IAP2 and XIAP in 30 peripheral blood samples from B-CLL patients (16 samples from untreated patients) and compared it to well-known prognosis factors such as clinical stage (Rai and Binet), lymphocyte doubling time, gender, age and previous chemotherapeutic treatment or not. High levels of c-IAP1 and XIAP expression were not associated with any prognosis factor. On the other hand, interestingly, high levels of c-IAP2 expression were correlated with advanced clinical stage (p = 0,021 and p= 0,031 for Rai and Binet respectively) and previous chemotherapeutic treatment (p = 0,043). Our results suggest that the analysis of c-IAP2 expression in B-CLL cells might be considered a powerful tool as a marker for poor prognostic and disease progression.