HIGH EXPRESSION OF BCL-2 MESSENGER-RNA AS A DETERMINANT OF POOR-PROGNOSIS IN ACUTE MYELOID-LEUKEMIA

Background. The bcl-2 oncoprotein is suggested to be directly involved in the emergence of drug resistance by disrupting or delaying the apo ptotic program and promoting tumor survival. Patients and methods. In order to define the clinical relevance of the bcl-2 mRNA expression in acute myeloid leukemia (AML) and its correlation to therapy outcome a nd prognosis, we analyzed 219 AML bone marrow (BM) samples, including 119 patients with de novo AML at presentation, 37 with AML following m yelodysplastic syndrome (MDS), as well as 42 BM samples of AML in rela pse and 21 in complete remission (CR) using RT-PCR. For performing qua ntitative measurements of bcl-2 mRNA, we developed a quantitative RT-P CR. Results. Bcl-2 mRNA was detectable in 133 of 156 (84%) patients at diagnosis and 40 of 42 (95%) at relapse. AML patients with high bcl-2 mRNA expression achieved lower CR rates than those with no or low exp ression. Concerning the long-term outcome, the overall (OS) and diseas e-free survival (DFS) was significantly worse in AML patients with hig h expression levels of bcl-2 mRNA. The three-year OS for all newly dia gnosed AML patients was 49% and 10% (P=0.028), respectively, and 71% a nd 15% (P=0.0004) for patients <60 years. Comparable significant diffe rences were observed for the DFS. In AML following MDS and patients >6 0 years, the bcl-2 expression was not associated with remission rate o r survival. Conclusions. The expression of bcl-2 mRNA may serve as a p rognostic factor predicting remission outcome and long-term prognosis in AML.