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 myelo id leukemia (AML). More recently, it has been shown that autonomous pr oliferation of blast cells in liquid culture was also predictive of po or prognosis. In a series of 72 adult AML cases at diagnosis, we studi ed by flow cytometry the expression of P170 and bcl-2 proteins, togeth er with autonomous growth of leukemic cells in liquid culture. Cases w ere classified as exhibiting no proliferation (N = 29), intermediate p roliferation (N = 25) and high proliferation (N = 18). We observed a s ignificant correlation between the percentage of cells in each sample expressing P170 and bcl-2. This was confirmed by double staining techn iques showing that both antigens were present in the same cells. We al so observed a significant association between growth pattern and P170 or bcl-2 expression. All patients were treated by intensive chemothera py including an anthracycline drug and cytarabine. The blasts of patie nts achieving complete remission (N = 47) were less frequently positiv e for CD34, P170 and bcl-2 than those from patients who did not. Growt h pattern also influenced significantly CR. In univariate analysis, CD 34, P170 and bcl-2 expression, as well as growth pattern, significantl y influenced survival. However, in multivariate analysis P170 expressi on remained the only significant factor, bcl-2 (or proliferation) havi ng no independent value. Our study confirms the prognostic value of P1 70 and bcl-2 expression as well as the value of spontaneous proliferat ion and suggests that several drug-resistance mechanisms are implicate d concomitantly in AML.