Combined analysis of bcl-2 and MDR1 proteins in 256 cases of acute myeloid leukemia

Abstract

BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the expression of MDR1 and bcl-2 proteins in de novo acute myeloid leukemia (AML). DESIGN AND METHODS: The expression of MDR1 and bcl-2 was analyzed by flow cytometry in a large series of 256 consecutive cases of AML. The results were recorded as percentage of positivity and relative mean fluorescence intensity (rMFI). To determine individual protein levels, an index which equals the product of the percentage of positive cells and rMFI was generated. RESULTS: Using cut-offs of >or=800 and 300 of the index value for bcl-2 and MDR1 expression, respectively, we identified 4 different classes of AML: 1) double negative; 2) single positive bcl-2+/MDR1-; 3) single positive bcl-2-/MDR1+; 4) double positive. The highest incidence of double negative cases was observed in the M2 class whereas double positive cases occurred more frequently in the M4, M5 and M6 subgroups. Seventy-eight percent and 71% of M0 and M1, respectively, showed single positive bcl-2+/MDR1- expression (p = 0.00001). Twenty-eight percent of patients belonging to the double positive category achieved complete remission, whereas for double negative, single positive bcl-2+MDR1- and single positive bcl-2-/MDR1+ category, the complete remission rate was 69%, 52% and 56%, respectively (p = 0.00038). In multivariate analysis, the double positive status independently affected frequency of complete remission (p = 0.008). INTERPRETATION AND CONCLUSIONS: Bcl-2 is over-expressed in CD34+ AML; conversely, MDR1 is over-expressed in CD34- AML. However, the combined expression of the two proteins defines a subset of AML with a very poor prognosis.