TY - JOUR
T1 - CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age
AU - van den Heuvel-Eibrink, Marry M.
AU - van der Holt, Bronno
AU - Burnett, Alan K.
AU - Knauf, Wolfgang U.
AU - Fey, Martin F.
AU - Verhoef, Gregor E.G.
AU - Vellenga, Edo
AU - Ossenkoppele, Gert J.
AU - Löwenberg, Bob
AU - Sonneveld, Pieter
PY - 2007/5
Y1 - 2007/5
N2 - Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/ MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients ≤60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p<0.05, p<0.001,p<0.001 and p<0.001). Higher BCRP mRNA was associated with secondary AML (p<0.05). MDR1 and BCRP mRNA were highly significantly associated (p<0.001), as were MRP1 and LRP mRNA (p<0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p=0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.
AB - Clinical resistance to chemotherapy in acute myeloid leukemia (AML) is associated with the expression of the multidrug resistance (MDR) proteins P-glycoprotein, encoded by the MDR1/ABCB1 gene, multidrug resistant-related protein (MRP/ABCC1), the lung resistance-related protein (LRP), or major vault protein (MVP), and the breast cancer resistance protein (BCRP/ABCG2). The clinical value of MDR1, MRP1, LRP/ MVP, and BCRP messenger RNA (mRNA) expression was prospectively studied in 154 newly diagnosed AML patients ≤60 years who were treated in a multicenter, randomized phase 3 trial. Expression of MDR1 and BCRP showed a negative whereas MRP1 and LRP showed a positive correlation with high white blood cell count (respectively, p<0.05, p<0.001,p<0.001 and p<0.001). Higher BCRP mRNA was associated with secondary AML (p<0.05). MDR1 and BCRP mRNA were highly significantly associated (p<0.001), as were MRP1 and LRP mRNA (p<0.001) expression. Univariate regression analyses revealed that CD34 expression, increasing MDR1 mRNA as well as MDR1/BCRP coexpression, were associated with a lower complete response (CR) rate and with worse event-free survival and overall survival. When adjusted for other prognostic actors, only CD34-related MDR1/BCRP coexpression remained significantly associated with a lower CR rate (p=0.03), thereby identifying a clinically resistant subgroup of elderly AML patients.
KW - BCRP
KW - Elderly AML
KW - Genes
KW - LRP
KW - MDR1
KW - MRP1
UR - http://www.scopus.com/inward/record.url?scp=33947594138&partnerID=8YFLogxK
U2 - 10.1007/s00277-007-0269-7
DO - 10.1007/s00277-007-0269-7
M3 - Article
C2 - 17340137
AN - SCOPUS:33947594138
SN - 1432-0584
VL - 86
SP - 329
EP - 337
JO - Annals of hematology
JF - Annals of hematology
IS - 5
ER -