Expression of Livin, an antiapoptotic protein, is an independent favorable prognostic factor in childhood acute lymphoblastic leukemia

Abstract

Livin, a member of the inhibitor of apoptosis proteins, has been considered to be a poor prognostic marker in malignancies. However, little is known about the clinical relevance of Livin expression in childhood acute lymphoblastic leukemia (ALL). In this study, the expression of Livin was analyzed in 222 patients with childhood ALL using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a possible association with the clinical features at diagnosis and treatment outcomes. Both Livin expression rates and expression levels were higher in patients with favorable prognostic factors. The expression rate was also higher in patients with a favorable day 7 bone marrow response to induction chemotherapy (P < .001). The Livin expression was related to the absence of relapse (P < .001). Similarly, the relapse-free survival rate (؎ 95% CI) was higher in patients with Livin expression than in patients without Livin expression (97.9% ؎ 4.0% versus 64.9% ؎ 11.8%, P < .001). Multivariate analysis for relapse-free survival demonstrated that Livin expression was an independent favorable prognostic factor in childhood ALL (P ‫؍‬ .049). This study suggests that Livin expression is a novel prognostic marker in childhood ALL and thus needs to be incorporated into the patient stratification and treatment protocols. (Blood. 2007;109: [471][472][473][474][475][476][477]

p21WAF1 modulates drug-induced apoptosis and cell cycle arrest in B-cell precursor acute lymphoblastic leukemia

“…Caspase activity can be inhibited by a range of cellular processes, such as high expression of Melanoma Inhibitor of Apoptosis Protein, overexpression of survivin, or even by binding of p21 WAF1 to procaspase-3. [43][44][45] T-ALL PDX cells were also sensitive to the death inducing effects of vorinostat, as determined by significantly lower IC 50 values compared to BCP-ALL PDXs. In comparison, the p21 WAF1 -defective T-ALL and p21 WAF1 -functional BCP-ALL PDXs demonstrated generally similar sensitivities to the p53-inducing agents, etoposide and nutlin-3.…”

Upregulation of the antiapoptotic factor Livin contributes to cisplatin resistance in colon cancer cells

“…Livin has been identified as a member of the IAP family [2][3][4]. Its expression spectrum includes melanoma, leukemias, bladder cancer, breast cancer, cervical cancer, nasopharyngeal cancer and lung cancer [5][6][7][8].…”

“…Due to its distinctive enrichment in tumors but none or low expression in normal tissue, Livin has been proposed as a potential therapeutic target [19]. Several reports helped to expand its expression profile to variant tumors such as melanoma, leukemias, bladder, breast, cervical, nasopharyngeal and lung cancer [5][6][7][8]. However, there are only limited reports regarding its expression in CRC except some preliminary studies [17][18][19][20][21].…”

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney

“…More recently, however, livin expression was also detected in various additional cancers, including leukaemias (Qiuping et al, 2004;Choi et al, 2007), bladder cancer (Gazzaniga et al, 2003), lung cancer (Tanabe et al, 2004;Hariu et al, 2005;Crnković-Mertens et al, 2006b), neuroblastoma (Kim et al, 2005), nasopharyngeal carcinoma (Xiang et al, 2006), astrocytoma (Liu et al, 2006), malignant pleural mesothelioma (Gordon et al, 2007), pancreatic cancer (Lopes et al, 2007), and renal cell carcinoma (RCC) (Crnković-Mertens et al, 2007). Notably, studies of biopsies from bladder cancer (Gazzaniga et al, 2003), lung cancer (Hariu et al, 2005), nasopharyngeal carcinoma (Xiang et al, 2006), malignant pleural mesothelioma (Gordon et al, 2007), and pancreatic cancer (Lopes et al, 2007) reported that Livin is typically expressed in the tumour samples, but not in the corresponding normal tissues.…”