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Expression of the multidrug resistance-associated protein in myelodysplastic syndromes
S Poulain1, P Lepelley, C Preudhomme
1Laboratoire d'Hématologie A, Centre Hospitalier Universitaire de Lille, France.
Abstract:
In the myelodysplastic syndromes (MDS), P-glycoprotein (P-gp) expression is clinically associated with drug resistance, whereas the clinical significance of multidrug resistance-associated protein (MRP1) is uncertain. Bone marrow from 56 patients with MDS, including six with refractory anaemia (RA)/RA with ringed sideroblasts (RARS), 23 cases of RA with excess blasts/in transformation (RAEB/T), four patients with chronic myelomonocytic leukaemia (CMML) and 23 cases of MDS having progressed to acute myeloid leukaemia (MDS-AML), were studied. MRP1 expression was investigated by immunocytochemistry (ICC) and by flow cytometry using MRPm6 monoclonal antibody. The efflux test using calcein-AM (CAM) +/- probenecid to evaluate MRP1 activity was performed in ten of the 56 patients. Twenty-eight of the 56 cases (50%) expressed MRP1. MRP1 expression was more frequent in MDS-AML than in MDS (70% vs. 36%). The efflux test using CAM was positive in three out of the ten patients tested. The results were in agreement with expression of MRP1 in six cases, and were discordant in four cases (1 MRP-/CAM+, 3 MRP+/CAM-). No correlation was observed between MRP1 expression and P-gp, lung resistance-associated protein (LRP) or CD34 expression, although there was a trend for more frequent MRP1 expression in P-gp-positive cases in MDS-AML (P = 0.08). Ten of the 26 patients treated with intensive chemotherapy achieved complete remission including six out of 16 MRP1+ and four out of ten MRP1- cases (P = NS). In conclusion, MRP1 expression was correlated with disease stage in MDS in our study. As for P-gp, discordant expression/function of MRP1 could be found in some cases, suggesting the existence of non-functional transport proteins in MDS. MRP1 expression did not seem to be a prognostic factor in MDS in our experience.
Insights
Multidrug resistance-associated protein 1 (MRP1) expression is linked to disease stage in myelodysplastic syndromes (MDS). While MRP1 expression was observed in 50% of patients, its role as a prognostic factor remains uncertain.
Area of Science:
- Hematology
- Molecular Biology
- Oncology
Background:
- P-glycoprotein (P-gp) is clinically associated with drug resistance in myelodysplastic syndromes (MDS).
- The clinical significance of multidrug resistance-associated protein 1 (MRP1) in MDS is not well-defined.
- Understanding drug resistance mechanisms in MDS is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the expression and potential clinical significance of MRP1 in patients with MDS.
- To compare MRP1 expression with P-glycoprotein (P-gp) and other markers.
- To assess the correlation between MRP1 expression and treatment response in MDS.
Main Methods:
- Immunocytochemistry (ICC) and flow cytometry were used to detect MRP1 expression in bone marrow samples from 56 MDS patients.
- An efflux test using calcein-AM (CAM) +/- probenecid was performed to evaluate MRP1 activity in a subset of patients.
- Expression levels were analyzed in relation to disease subtypes, P-gp, LRP, CD34 expression, and chemotherapy response.
Main Results:
- MRP1 was expressed in 50% of MDS cases (28/56), with higher frequency in MDS-AML (70%) compared to other MDS subtypes (36%).
- MRP1 activity (efflux test) showed discordant results with protein expression in some cases, suggesting potential non-functional transporters.
- No significant correlation was found between MRP1 expression and P-gp, LRP, or CD34 expression, nor with complete remission rates after chemotherapy.
Conclusions:
- MRP1 expression is correlated with disease stage in myelodysplastic syndromes.
- Discordant MRP1 expression and function were observed, indicating potential non-functional transporters in MDS.
- MRP1 expression did not appear to be a prognostic factor for MDS in this study.