[Multidrug resistance in chronic lymphocytic leukemia.]

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[Multidrug resistance in chronic lymphocytic leukemia.]

T Szendrei, T Magyarlaki, G Kovacs, A Nagy, A Szomor, L Molnar, M , M

Tokes-Fuzesi, O Rideg, L Poto, L Pajor, B Kajtar, and H Losonczy

Orv Hetil, January 27, 2008; 149(4): 161-7.

Pécsi Tudományegyetem, Orvostudományi és Egészségtudományi Centrum I.

Belgyógyászati Klinika, Hematológiai Osztály Pécs Ifjúság u. 13. 7624.

[Hungary]

Introduction: New prognostic factors discovered in chronic lymphocytic leukemia

have recently got into the center of clinical interest. While the predictive

value of cytogenetical abnormalities, immunglobulin heavy chain gene mutation

status, CD38 and ZAP70 expression is already well known, the significance of

multidrog resistance in chronic lymphocytic leukemia is not well characterized.

Aims: 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 mounths) 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.

PMID: 18201958