title: Application of flow cytometry immunophenotyping and multidrug resistance assay in B-cell acute lymphoid leukemia and multiple myeloma.
abstract: Multidrug resistance is one of the mechanisms how to explain failure of chemotherapy in patients with different hematological malignancies. In this study we aimed to evaluate and compare the drug resistance in B-cell acute lymphoid leukemia (B-ALL) and multiple myeloma (MM) in association with their immunophenotypes and genotypes. Eleven patients with B-ALL and 14 patients with MM were classified according to prognostic factors. Standard MoAb panel for ALL and triple labeled antibodies (CD38/CD56/CD19) and detection of intracellular light chains for MM were used. Flow cytometric calcein assay was performed for measure of P- glycoprotein (MDR-1) and multidrug resistance associated protein (MRP-1) activity. Markers CD19, CD20 and HLA-DR proved to be useful in identifying cells of B-lymphoid lineage. CD34 progenitor cell antigen was present in high proportion of ALL blasts. Both the abnormal plasmacell populations and their monoclonality in MM were confirmed by immunophenotyping, too. The mean MDR activity factor (MAF) values were not different in patients with MM and B- ALL. However, the mean MRP-1 values in MM were significantly lower than MAF-MDR-1 (1.85+/-3.8 versus 5.92+/-7.45, p=0.05), but we have found lower values in refractory conditions as expected from previous studies of acute myeloid leukemia. The immunophenotyping was helpful in detection of abnormal populations showing no correlation with the MDR. However, in this study we could not confirm high MDR activity despite of the failure of chemotherapy. The calcein assay seems to be useful for quantitative and sensitive measurement of the MDR proteins. The low activity of MDR- 1 and MRP-1 in MM need further clarification, indicating the involvement of different transport in the resistance mechanism.
authors.affiliation: Institute of Hematology and Immunology, National Medical Centre, Budapest, Hungary. kjakab@ohvi.hu
authors.forename: K
authors.initials: K
authors.lastname: Jakab
authors.forename: L
authors.initials: L
authors.lastname: Gopcsa
authors.forename: E
authors.initials: E
authors.lastname: Adam
authors.forename: G
authors.initials: G
authors.lastname: Domjan
authors.forename: B
authors.initials: B
authors.lastname: Sarkadi
authors.forename: K
authors.initials: K
authors.lastname: Paloczi
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D018432:Drug Resistance, Multiple; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor