Overexpression of the p73 gene is a novel finding in high-risk B-cell chronic lymphocytic leukemia

The p73 protein shares structural and functional similarities with the tumo ur-suppressor p53, but its role in neoplastic transformation is unknown. Al ternative splicing leads to the expression of at least nine p73 C-terminal mRNA splice variants (alpha, beta, gamma, delta, epsilon, zeta, eta, eta1, theta). In this survey, we analyse the expression of p73 by real-time quant itative RT-PCR, its known C-terminal variants with an RT-PCR-Southern techn ique and by Western blot in samples of 51 patients with B-CLL, normal B lym phocytes from eight individuals, and five haematopoetic cell lines. p73 alp ha protein expression positively correlated with higher risk B-CLL stages ( P = 0.046). Total p73 mRNA expression was higher (P = 0.01) and p73 alpha p rotein more frequently detected (P = 0.008) in B-CLL compared with normal C D19+-B-lymphocytes. p73 C-terminal mRNA variants were expressed both in B-C LL and in normal B-lymphocytes, but their expression was biased since the g amma (P = 0.041), the theta (P < 0.001), and the eta variant (P = 0.033) pr evailed in normal B-lymphocytes. In summary, we conclude that the accumulat ion of p73, the expression pattern of particular p73 variants and its link to progression may play a distinct role in the molecular pathology B-CLL.