Document Detail


Evaluation of the clinical relevance of the expression and function of P-glycoprotein, multidrug resistance protein and lung resistance protein in patients with primary acute myelogenous leukemia.
MedLine Citation:
PMID:  11755464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The multidrug resistance (MDR) transporter-proteins P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance protein (LRP) have been associated with treatment failure. The aim of this study was to investigate prospectively the clinical significance of expression and function of the MDR proteins, considering other prognostic factors, such as age, immunophenotype, and cytogenetics. Mononuclear cells of peripheral blood or bone marrow from 61 patients with de novo acute myelogenous leukemia (AML) were analyzed. The monoclonal antibodies JSB1, MRPm6 and LRP56 were used for expression studies. Accumulation and retention studies were performed using the substrates Daunorubicin, Calcein-AM, Rhodamine-123 and DiOC(2) in the presence or absence of the modifiers Verapamil, Genistein, Probenecid, BIBW22S and PSC833. Induction treatment consisted of a 3+7 combination of Ida/Ara-C for patients < or = 60 years of age and a 3+5 Ida/VP-16 combination per OS for patients >60. MDR function was expressed as the ratio of mean fluorescence intensity substrate in the presence of modifier over the substrate alone (resistance index, RI). Patients with advanced age, low CD15 expression and high RI for accumulation of DiOC(2) in the presence of BIBW22S had significantly lower complete remission (CR) rates. No factor was prognostic for event-free survival analysis, which was limited to remitters only. Overall survival was shorter in patients with advanced age, poor prognosis cytogenetics, high CD7 expression, and high RI for Daunorubicin efflux modulated by Verapamil. These results suggest that MDR transporter-proteins have a limited role in the treatment failure of patients treated with Idarubicin-based regimens.
Authors:
Apostolia Maria Tsimberidou; George Paterakis; George Androutsos; Nikolaos Anagnostopoulos; Athanasios Galanopoulos; Themistoklis Kalmantis; John Meletis; Yiannis Rombos; Alexandros Sagriotis; Argyrios Symeonidis; Maria Tiniakou; Nikolaos Zoumbos; Xenophon Yataganas
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Leukemia research     Volume:  26     ISSN:  0145-2126     ISO Abbreviation:  Leuk. Res.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2001-12-28     Completed Date:  2002-03-27     Revised Date:  2006-10-03    
Medline Journal Info:
Nlm Unique ID:  7706787     Medline TA:  Leuk Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  143-54     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, The University of Athens, Athens 11527, Greece. atsimber@mail.mdanderson.org
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adolescent
Adult
Age Factors
Aged
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Bone Marrow Transplantation
Calcium Channel Blockers / pharmacology
Carbocyanines / metabolism
Combined Modality Therapy
Cytarabine / administration & dosage
Daunorubicin / metabolism
Disease-Free Survival
Drug Resistance, Multiple / genetics*
Drug Resistance, Neoplasm / genetics*
Enzyme Inhibitors / pharmacology
Female
Fluoresceins / metabolism
Fluorescent Dyes / metabolism
Genistein / pharmacology
Humans
Idarubicin / administration & dosage
Immunophenotyping
Leukemia, Myeloid / drug therapy,  genetics,  metabolism*,  mortality,  therapy
Male
Middle Aged
Multidrug Resistance-Associated Proteins / biosynthesis,  genetics,  physiology*
Neoplasm Proteins / biosynthesis,  genetics,  physiology*
P-Glycoprotein / biosynthesis,  genetics,  physiology*
Probenecid / pharmacology
Prognosis
Prospective Studies
Rhodamine 123 / metabolism
Survival Analysis
Tumor Cells, Cultured / metabolism
Vault Ribonucleoprotein Particles / biosynthesis,  genetics,  physiology*
Verapamil / pharmacology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Carbocyanines; 0/Enzyme Inhibitors; 0/Fluoresceins; 0/Fluorescent Dyes; 0/Multidrug Resistance-Associated Proteins; 0/Neoplasm Proteins; 0/P-Glycoprotein; 0/Vault Ribonucleoprotein Particles; 0/major vault protein; 0/multidrug resistance-associated protein 1; 147-94-4/Cytarabine; 148504-34-1/calcein AM; 20830-81-3/Daunorubicin; 37069-75-3/3,3'-diethyloxacarbocyanine; 446-72-0/Genistein; 52-53-9/Verapamil; 57-66-9/Probenecid; 58957-92-9/Idarubicin; 62669-70-9/Rhodamine 123

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