HIGH BCL-2 EXPRESSION IN ACUTE MYELOID-LEUKEMIA CELLS CORRELATES WITHCD34 POSITIVITY AND COMPLETE REMISSION RATE

Flow cytometric expression of bcl-2 protein was analyzed in 90 newly d iagnosed acute myeloblastic leukemia (AML) patients using an anti-bcl- 2 monoclonal antibody by direct immunofluorescence technique and resul ts were correlated with FAB cytotype, CD34 expression and clinical out come. Bcl-2 was expressed in all AML cases with different intensity. T he mean fluorescence index (MFI), expressed as the ratio of sample mea n channel:control mean channel, ranged from 3.0 to 39.5 with a median value of 14. The MFI was significantly higher (P = 0.01) in M0 (20.9) and M1 (18.3) than in M2 (11.7), M3 (12.4), M4 (11.8) and M5 (9.5) cyt otypes. In addition, bcl-2 MFI significantly correlated both with CD34 positivity (P = 0.001) and with CD34 MFI (P = 0.O1), being CD34 antig en expressed in 65% of patients with a bcl-2 MFI > 14, and only in 35% of AML cases with a bcl-2 MFI > 14. When bcl-2 intensity expression w as correlated with complete remission (CR) rate, a higher MFI was asso ciated with a low CR rate after standard intensive chemotherapy. In pa rticular, CR was achieved in 86% of patients with a bcl-2 MFI < 14, bu t only in 57% of patients with a MFI > 14 (P = 0.008). A further decre ase of CR rate to 41% was observed in patients in whom a higher bcl-2 MFI was coupled with the presence of CD34 antigen on their blasts. By statistical analysis we also demonstrated that both bcl-2 high MFI (> 14) and CD34 expression are independent prognostic factors for achievi ng CR in AML. These data raise the hypothesis that high values of bcl- 2 may confer on myeloid blasts a higher resistance to standard chemoth erapy. However, identification of patients with high expression of bcl -2 may be important for a different therapeutic approach.