TY - JOUR
TI - 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
AU - Tsimberidou, AM
AU - Paterakis, G
AU - Androutsos, G
AU - Anagnostopoulos,
AU - N
AU - Galanopoulos, A
AU - Kalmantis, T
AU - Meletis, J
AU - Rombos, Y and
AU - Sagriotis, A
AU - Symeonidis, A
AU - Tiniakou, M
AU - Zoumbos, N and
AU - Yataganas, X
JO - Leukemia Research
PY - 2002
VL - 26
TODO - 2
SP - 143-154
PB - PERGAMON-ELSEVIER SCIENCE LTD
SN - 0145-2126
TODO - 10.1016/S0145-2126(01)00106-0
TODO - P-glycoprotein; multidrug resistance protein; lung resistance protein;
primary acute myelogenous leukemia
TODO - 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 less than or equal to 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. (C) 2002 Elsevier Science Ltd. All rights
reserved.
ER -