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Loss of DCC Gene Expression Is of Prognostic Importance in Acute Myelogenous Leukemia

Division of Hematology, Department of Internal Medicine and Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo 113-8603, Japan

Purpose: Expression of the deleted in colorectal carcinoma (DCC) gene has been found to be lost in some patients with acute myelogenous leukemia (AML). Although this finding is critical to leukemogenesis, its prognostic significance remains uncertain. To evaluate this, loss of DCC gene expression in AML patients and their prognostic significance were investigated.

Experimental Design: A group of 170 patients with AML was analyzed. DCC gene expression in AML cells was determined by a semiquantitative reverse transcriptase-PCR. Simultaneous mutation analyses of the p53, N-ras, and FLT3 genes were performed in all of the AML cells by single-strand conformation polymorphism and sequencing subsequent to PCR. The importance of loss of DCC expression was evaluated by Cox proportional analysis and the Kaplan-Meier method.

Results: Loss of DCC expression was detected in 47 patients (27.6%). The p53, N-ras, and FLT3 mutations were detected in 20 (11.7%), 42 (24.7%), and 26 (15.2%) patients, respectively. The durations of overall survival (OS) and complete remission (CR) of the 47 DCC-negative AML patients were significantly shorter than that of the 123 DCC-positive patients (P < 0.0045 and <0.0060, respectively). Univariate and multivariate analyses showed that loss of DCC expression was an unfavorable prognostic factor for both OS (P < 0.0053 and <0.0084, respectively) and CR duration (P < 0.0146 and <0.0371, respectively). The 64 DCC-positive patients with wild p53, N-ras, and FLT3 had statistically better CR attainment compared with the other 106 patients (P < 0.0001).

Conclusions: Loss of DCC gene expression was shown to be an independent prognostic factor in AML patients. Thus, loss of DCC gene expression might serve as an important molecular marker for predicting the CR duration and OS of patients with AML.

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