Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias

Expression of several inhibitor of apoptosis proteins (IAPs) was investigat ed in the National Cancer Institute panel of 60 human tumor cell lines, and the expression and prognostic significance of one of these, XIAP, was eval uated in 78 previously untreated patients with acute myelogenous leukemia ( AML). XIAP and cIAP1 were expressed in most cancer Lines analyzed, with sub stantial variability in their relative levels, In contrast, NAIP mRNA was n ot detectable, and cIAP2 was found at the mRNA and protein levels in only 3 4 (56%) and 5 (8%) of the 60 tumor cell lines analyzed, respectively. Inter estingly, XIAP, cIAP1, and cIAP2 mRNA levels did not correlate with protein levels in the tumor lines, indicating posttranscriptional regulation of ex pression High levels of XIAP protein in tumor cell lines were unexpectedly correlated with sensitivity to some anticancer drugs, particularly cytarabi ne and other nucleosides, whereas higher level; of cIAP1 protein levels wer e associated with resistance to several anticancer drugs. The relevance of XIAP to in vivo responses to cytarabine was explored in AML, making correla tions with patient outcome (n = 78), Patients with lower levels of XIAP pro tein had significantly longer survival (median, 133 versus 52.5 weeks; P = 0.05) and a tendency toward longer remission duration (median, 87 versus 52 .5 weeks; P = 0.13) than those with higher levels of XIAP. Altogether, thes e findings show that IAPs are widely but differentially expressed in human cancers and leukemias and suggest that higher XIAP protein levels may have adverse prognostic significance for patients with AML.