title: Multidrug resistance analysis in lymphoproliferative disease of large granular lymphocytes.
abstract: Multi-drug resistance (MDR) phenotype contributes to the ineffectiveness of chemotherapy. P-glycoprotein (PgP) and lung resistance protein (LRP) are proteins implicated in chemoresistance. We analysed the expression of PgP and LRP respectively in 17 and 15 cases of lymphoproliferative disease of granular lymphocytes (LDGL) including 10 cases of clonal large granular lymphocytic (LGL) leukaemia, six cases of oligoclonal (n = 5) and polyclonal (n = 1) CD3+ lymphoproliferation and one case of CD3- NK lymphocytosis. Functional PgP activity, as determined by Rh123 dye efflux assay, was found in all the patients. The mean percentage of effluxing cells was 47 +/- 22%, compared to 35 +/- 8% on normal lymphocytes (P<0.04). The efflux was blocked in the presence of verapamil, a PgP revertant agent. A high proportion of CD57+ cells (66 +/- 10%) from these patients expelled Rh123. Functional PgP activity was associated with expression of MDR1 mRNA. By using immunocytochemistry, LRP expression was detected in 11/15 patients (73%). 7/10 LGL leukaemia patients presented a LRP+/Efflux+ phenotype and 5/7 had LRP+/Efflux+/MDR1 mRNA+ phenotype. These findings suggest that the PgP+/LRP+ phenotype is frequently observed in LDGL. Its clinical relevance in aggressive cases remains to be determined.
authors.affiliation: Department of Hematology-Oncology, H. Lee Moffitt Cancer Center, Tampa, Florida 33612, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lamy
authors.forename: B
authors.initials: B
authors.lastname: Drenou
authors.forename: O
authors.initials: O
authors.lastname: Fardel
authors.forename: L
authors.initials: L
authors.lastname: Amiot
authors.forename: I
authors.initials: I
authors.lastname: Grulois
authors.forename: P Y
authors.initials: PY
authors.lastname: Le Prise
authors.forename: T P
authors.initials: TP
authors.lastname: Loughran
authors.forename: R
authors.initials: R
authors.lastname: Fauchet
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005260:Female; D019450:Genes, MDR; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015703:Antigens, CD; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein