IN ACUTE MYELOID-LEUKEMIA, COEXPRESSION OF AT LEAST 2 PROTEINS, INCLUDING P-GLYCOPROTEIN, THE MULTIDRUG RESISTANCE-RELATED PROTEIN, BCL-2, MUTANT P53, AND HEAT-SHOCK-PROTEIN-27, IS PREDICTIVE OF THE RESPONSE TO INDUCTION CHEMOTHERAPY

To identify prognostic factors alternative or additional to P-glycopro tein (Pgp), we studied the impact of the multidrug resistance-related protein (MRP), bcl-2 (flow cytometry), mutant p53 (single-strand confo rmation polymorphism), and heat-shock protein 27 (HSP27, Western blott ing) in myeloid blasts obtained at the time of diagnosis in patients w ith de novo acute myeloid leukemia (AML). We collected bone marrow sam ples from untreated AML patients, prepared the cells as well as the ce llular protein, and froze all the material. We then analyzed 20 patien ts who responded with complete remission (CR) and 20 patients who had blast persistence (BP). The purpose of the study was to determine whet her leukemic blasts from patients with BP were more resistant to chemo therapy than those from patients with CR. There was no significant cor relation between the expression of any of these proteins alone and tre atment outcome in both groups studied. In contrast, there was a signif icant correlation between the coexpression of at least two of these pr oteins and response (p = 0.0298), which turned out to be a significant independent prognostic factor for treatment failure (p = 0.0329, rela tive risk = 1.5) according to multivariate analysis. We conclude that drug resistance in AML is multifactorial. Thus, coexpression of differ ent resistance mechanisms may be responsible for the primary drug resi stance in de novo AML.