CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age

van den Heuvel-Eibrink, M. M., van der Holt, B., Burnett, Alan Kenneth, Knauf, W. U., Fey, M. F., Verhoef, G. E., Vellenga, E., Ossenkoppele, G. J., Lowenberg, B. and Sonneveld, P. 2007. CD34-related coexpression of MDR1 and BCRP indicates a clinically resistant phenotype in patients with acute myeloid leukemia (AML) of older age. Annals of Hematology 86 (5) , pp. 329-337. 10.1007/s00277-007-0269-7

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Abstract

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 >or=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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	ATP Binding Cassette Transporters / metabolism*,Acute Disease, Age Factors, Aged, Antigens CD34 / metabolism, Disease Free Survival, Drug Resistance Neoplasm / genetics*, Humans, Leukemia Myeloid / drug therapy*, Leukemia Myeloid / genetics, Leukemia Myeloid / metabolism*, Middle Aged, Multi drug Resistance Associated Proteins / metabolism*, Neoplasm Proteins / metabolism*, Phenotype, Prospective Studies, RNA Messenger / metabolism, Vault Ribonucleoprotein Particles / metabolism Substances ABCG2 protein, human Antigens, CD34 Multidrug Resistance-Associated Proteins Neoplasm Proteins RNA, Messenger Vault Ribonucleoprotein Particles major vault protein multidrug resistance-associated protein
Additional Information:	Publication Types Clinical Trial, Phase III Randomized Controlled Trial Full Text Sources Springer EBSCO Europe PubMed Central Gale Databases Ingenta plc Ovid Technologies, Inc. ProQuest PubMed Central PubMed Central Canada Miscellaneous See the articles recommended by F1000Prime's Faculty of more than 5,000 expert scientists and clinical researchers. - Faculty of 1000
Publisher:	Springer Verlag
ISSN:	0939-5555
Last Modified:	25 Jun 2017 04:43
URI:	https://orca.cardiff.ac.uk/id/eprint/59146

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