Overexpression of Apollon, an Antiapoptotic Protein, Is Associated with Poor Prognosis in Childhood De novo Acute Myeloid Leukemia

Abstract

The genes that encode inhibitor of apoptosis proteins are frequently overexpressed in human cancers and can be associated with resistance to therapy. The overexpression of Apollon, a member of inhibitor of apoptosis proteins, is intuitively expected to be associated with unfavorable clinical features in malignant diseases; however, there have been no clinical studies reporting the prognostic relevance of Apollon expression in human malignancies. This study was done to investigate the clinical relevance of the expression of Apollon in childhood de novo acute myeloid leukemia. In 55 pediatric patients with de novo acute myeloid leukemia, the level of Apollon expression was determined by using quantitative reverse transcriptase-PCR and was analyzed with respect to the patients' clinical features and treatment outcomes. Apollon expression was found to be higher in patients with a leukocyte number of >or=10,000/microL, patients with extramedullary disease, and patients with the French-American-British classification subtype M7. In addition, Apollon overexpression (>or=median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poorer 3-year relapse-free survival rate (48.3 +/- 11.2% versus 78.7 +/- 8.5%, P = 0.040). This is the first study demonstrating the prognostic implication of the Apollon expression in human cancers, indicating that Apollon overexpression may be used as a poor prognostic marker in childhood acute myeloid leukemia through validation by further studies.