Simultaneous expression of P-glycoprotein and BCL-2 in acute myeloid leukemia blast cells

High expression of the multidrug resistance gene product P170, and of the oncoprotein bcl-2 have been associated with in vitro resistance to chemotherapeutic agents and with poor clinical outcome in acute myeloid leukemia (AML). More recently, it has been shown that autonomous proliferation of blast cells in liquid culture was also predictive of poor prognosis. In a series of 72 adult AML cases at diagnosis, we studied by flow cytometry the expression of P170 and bcl-2 proteins, together with autonomous growth of leukemic cells in liquid culture. Cases were classified as exhibiting no proliferation (N = 29), intermediate proliferation (N = 25) and high proliferation (N = 18). We observed a significant correlation between the percentage of cells in each sample expressing P170 and bcl-2. This was confirmed by double staining techniques showing that both antigens were present in the same cells. We also observed a significant association between growth pattern and P170 or bcl-2 expression. All patients were treated by intensive chemotherapy including an anthracycline drug and cytarabine. The blasts of patients achieving complete remission (N = 47) were less frequently positive for CD34, P170 and bcl-2 than those from patients who did not. Growth pattern also influenced significantly CR. In univariate analysis, CD34, P170 and bcl-2 expression, as well as growth pattern, significantly influenced survival. However, in multivariate analysis P170 expression remained the only significant factor, bcl-2 (or proliferation) having no independent value. Our study confirms the prognostic value of P170 and bcl-2 expression as well as the value of spontaneous proliferation and suggests that several drug-resistance mechanisms are implicated concomitantly in AML.