Prognostic Significance of Multidrug Resistance Proteins Expression in Acute Myeloid Leukemia.

Background: Conventional induction chemotherapy induces complete remission (CR) in 65–75% of adults with de novo acute myeloid leukemia (AML), and 15–20% of the patients have refractory disease. We investigated the prognostic significance of multidrug resistance proteins (P-glycoprotein (Pgp), BCRP, MRP1 and LRP) expression on AML blast cells before treatment.

Methods: We included in analysis 30 patients (pts) with de novo AML. Expression of multidrug resistance proteins (MDR) was detected by indirect immunofluorescence technique and flow cytometry on bone marrow blast cells before chemotherapy. Expression of MDR proteins was considered as positive if at least 25% of the blast cells were stained by anti-MDR protein antibody. All pts received standard induction therapy (cytarabine, etoposide and idarubicin or daunorubicine).

Results: Blast cells was defined as Pgp-positive in 64.3% of cases, BCRP+ in 42.9%, MRP1+ in 46.4%, and LRP+ in 64.3% of cases. After induction therapy 20 (66,7%) pts achieved CR and 10 pts (33.3%) were resistant. MDR proteins expression was observed more frequently in resistant group, then in a sensitive one (70% vs 61% for Pgp, 70% vs 33% for MRP1, 100% vs 44% for LRP, 80% vs 22% for BCRP, respectively), difference for LRP and BCRP was statistically significant (p=0.004). Blast cells of all resistant pts expressed 2–4 MDR proteins (all studied proteins − 40%, 3 of them − 40% and 2 proteins − 20%). In a group of pts archived CR the blast cells expressed 3 proteins only in 2 cases (10%), and the expression of all 4 proteins we observed only in 1 patient (5%) with very short CR duration (3 months). Other pts from this group express only one studied protein.

According to chromosome analysis 18.2% of pts had favorable, 50% - intermediate and 31.8% unfavorable cytogenetic. Blast cells of all pts in cytogenetically unfavorable group expressed more then 1 protein, 3 or 4 MDR proteins expressed in 71,4% of cases. In favorable and intermediate cytogenetic groups blast cells expressed 1or 2 MDR proteins in 73,2% of cases, 3 or 4 proteins in 20%.

Conclusions: The expression of MDR proteins in AML has a prognostic value with respect to CR achievement in pts receiving standard antracycline-Ara-C regimens. The detection of any single protein didn’t have prognostic significance, only co-expression of 2 and more proteins predict unfavorable treatment outcome. We observed a correlation between the cytogenetic and the MDR phenotype.