MLAA-34 is a newly identified monocytic leukemia-associated antigen. Previous data indicated that MLAA-34 might be a novel anti-apoptosis factor related closely to carcinogenesis or progression of acute monocytic leukemia. The over-expression of MLAA-34 is intuitively expected to be associated with unfavorable clinical features in acute myeloid leukemia. However, there have been no clinical studies about the prognostic relevance of MLAA-34 expression in human malignancies. This study was done to investigate the clinical relevance of the expression of MLAA-34 in de novo acute myeloid leukemia. In 126 patients with de novo acute myeloid leukemia, the level of MLAA-34 expression and protein expression ratio were determined by using quantitative reverse transcriptase-PCR and western blot, respectively. The results were analyzed with respect to the patients' clinical features and treatment outcomes. Both MLAA-34 expression rates and expression levels were found to be higher in patients with the French-American-British classification subtype M5, and the expression levels were also higher in patients with a leukocyte number of ≥ 20 × 10(9)/L and patients with extramedullary disease. In addition, MLAA-34 over-expression (≥ median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poor survival rate. In multivariate analysis, high MLAA-34 levels was independently associated with a poorer relapse-free survival and overall survival in AML patients. In conclusion, our data indicate that MLAA-34 may be used as a prognostic marker for treatment decision-making in acute monocytic leukemia through validation by further studies.