P-glycoprotein and terminal transferase expression identify prognostic subsets within cytogenetic risk classes in acute myeloid leukemia

Abstract Clinical and biological features were assessed in 204 consecutive de novo adult acute myeloid leukemia (AML) patients who received intensive chemotherapy regimens. Multiparameter flow cytometric assays both of the multidrug resistance (MDR-1)-associated P-glycoprotein (PGP) using the UIC2 monoclonal antibody (MoAb), and of terminal transferase (TdT) were performed. Cytogenetic findings were obtained from 196 patients with high resolution banding. At onset, UIC2 and TdT positivities were detected in 58.5% and 24% of cases, respectively. There were strict correlations either between UIC2 negativity and FAB M3 or between TdT and FAB M0-M1 ( P =0.001 and P P P P P P =0.001, respectively). The survival rates (Kaplan–Meier method) were significantly shorter either in UIC2+ or in TdT+ patients ( P =0.005 and =0.011, respectively). UIC2 and TdT negative cases showed longer remission duration ( P =0.03 and =0.22, respectively). The additional effect of UIC2 and TdT on prognosis allowed us to identify two subsets of patients, the first [UIC2−TdT−] at better and the second [UIC2+TdT+] at worse clinical outcome compared to single UIC2 and TdT cases, concerning CR ( P P P =0.007). The combinations [UIC2+TdT−] and [UIC2−TdT+] showed an intermediate clinical course. A strong difference was found between poor risk and intermediate/favorable risk cytogenetic classes with regard to CR rate ( P P P =0.005), survival ( P =0.02) and CR duration ( P =0.015). On the other hand, UIC2 and TdT negativity allowed us to distinguish patients with longer survival ( P =0.012 and =0.04, respectively) and CR duration ( P =0.04 and =0.025, respectively) within the intermediate/favorable risk class. The independent prognostic value of UIC2, TdT and cytogenetic risk classes was confirmed in multivariate analysis. These results suggest that PGP and TdT expressions, together with cytogenetic findings, may represent a basic predictor of chemotherapeutic failure in AML.