title: The relevance of multidrug resistance-associated P-glycoprotein expression in the treatment response of B-cell chronic lymphocytic leukemia.
abstract: OBJECTIVE
  The aim of this study was to determine whether expression of P-glycoprotein (Pgp) is an intrinsic feature of B-lymphocytes in B-cell chronic lymphocytic leukemia (B-CLL) and how it correlates with hematologic indices and tumor load in the disease. Furthermore, the change of Pgp expression under cytotoxic treatment and its correlation to treatment outcome were studied.
  
  
  METHODS
  In 42 B-CLL patients, of whom 13 were sequentially monitored, expression of extracellular (MRK-16) and intracellular (C-219) Pgp epitopes on peripheral blood lymphocytes was determined by flow cytometry analysis and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis.
  
  
  RESULTS
  Median RMF values in B-CLL patients were higher than in age-matched controls. Pgp expression did not correlate with any of the hematologic features or clinical stage of the disease. Patients who received some type of cytoreductive treatment prior to the study had lower Pgp values for both measured epitopes (median RMF for C-219 and MRK-16 of 1.99 and 2.03 in comparison to those of non-treated patients: 3.11 and 2.88, respectively). In 13 patients monitored during treatment the decrease in RMF was noted after treatment with chlorambucil, with RMF values for both Pgp epitopes decreasing in responders. This was in contrast to unchanged or even increased RMF values in those patients who did not respond to therapy.
  
  
  CONCLUSIONS
  Our study confirms the importance of quantitative evaluation of Pgp expression by flow cytometry. At the clinical level, cross-sectional, single test evaluation of Pgp is of limited value whereas sequential follow-up values correlate with treatment response.
authors: Cellular Immunology Department, Institute of Immunology, Zagreb, Croatia. ivna.svoboda-beusan@imz.tel.hr
authors: I
authors: I
authors: Svoboda-Beusan
authors: R
authors: R
authors: Kusec
authors: K
authors: K
authors: Bendelja
authors: I
authors: I
authors: Tudoric-Ghemo
authors: B
authors: B
authors: Jaksic
authors: V
authors: V
authors: Pejsa
authors: S
authors: S
authors: Rabatic
authors: B
authors: B
authors: Vitale
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000367:Age Factors; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D018432:Drug Resistance, Multiple / Q000235:genetics; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1