[Multidrug resistance in chronic lymphocytic leukemia].
BACKGROUND
New prognostic factors discovered in chronic lymphocytic leukemia have recently got into the center of clinical interest. While the predictive value of cytogenetical abnormalities, immunoglobulin heavy chain gene mutation status, CD38 and ZAP70 expression is already well known, the significance of multi-drug resistance in chronic lymphocytic leukemia is not well characterized.


OBJECTIVE
The goal of this study was to characterize the multidrug resistance features in 82 patients with chronic lymphocytic leukemia at the genetical, expression- and functional level and to compare it with the patient's clinical behavior (survival and response to therapy).


METHODS
Light Cycler Real Time PCR based "Single Nucleotide Polymorphism" analysis of the MDR1 gene, as a biological predictor of the expression level of P-glycoprotein was tested in 66 patients with chronic lymphocytic leukemia. P-glycoprotein expression and MDR-function was detected in 82 cases by flow cytometry (by use of anti-P-glycoprotein monoclonal antibody and calcein-verapamil functional test). Response to therapy was analyzed by statistical Fisher-test in the treated 35 patients. The survival analysis (Log-rank test) was performed on the whole population ( n = 82).


RESULTS
No significant correlation was found between the three levels of multidrug resistance (genetics, phenotype, function) in our patients with chronic lymphocytic leukemia. P-glycoprotein positive cases (n = 9) were predominantly non-responders (8/9, 89%). There must be, however, other mechanisms causing non-response (total non-responders: 13/35 treated cases). Most of P-glycoprotein negative CLL patients (n = 26) responded well (21/26, 80%) to chemotherapy (responders: 22/35 treated CLL) (p < 0,001). The tendency was the same in the average expected survival rate between P-glycoprotein positive and negative patients (84 vs 203 months) but the difference was not significant (p = 0,106).


CONCLUSIONS
This study proved the clinical prognostic significance of P-glycoprotein expression of leukaemic cells predicting the chemotherapy response and partially estimating the general survival of patients suffering from chronic lymphocytic leukemia.
Szendrei
Tamás
T
Pécsi Tudományegyetem, Orvostudományi és Egészségtudományi Centrum I Belgyógyászati Klinika, Hematológiai Osztály, Pécs, Hungary. tomasso81@freemail.hu
Magyarlaki
Tamás
T
Kovács
Gábor
G
Nagy
Agnes
A
Szomor
Arpád
A
Molnár
Lenke
L
Dávid
Mariann
M
Tokés-Füzesi
Margit
M
Rideg
Orsolya
O
Pótó
László
L
Pajor
László
L
Kajtár
Béla
B
Losonczy
Hajna
H
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor