Polymorphisms in transporter and phase II metabolism genes as potential modifiers of the predisposition to and treatment outcome of de novo acute myeloid leukemia in Israeli ethnic groups

Abstract Drug metabolism/disposition and transporter genes may influence predisposition or prognosis of AML (acute myeloid leukemia) patients. We analyzed polymorphisms in 3 transporters and 4 drug metabolism genes in 293 Israeli individuals (112 AML patients and 181 controls). We analyzed: ABCC3 (M...

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Veröffentlicht in:	Leukemia research 2008-06, Vol.32 (6), p.919-929
Hauptverfasser:	Müller, Phillip, Asher, Nava, Heled, Maya, Cohen, Sara Bar, Risch, Angela, Rund, Deborah
Format:	Artikel
Sprache:	eng
Schlagworte:	ABC transporters Adolescent Adult Aged Aged, 80 and over Alleles Arylamine N-Acetyltransferase - genetics ATP Binding Cassette Transporter, Sub-Family G, Member 2 ATP-Binding Cassette Transporters - genetics Biomarkers, Tumor - genetics Chemotherapy resistance DNA Primers Female Genetic Predisposition to Disease Genotype Glutathione Transferase - genetics GSTM1 GSTT1 Hematology, Oncology and Palliative Medicine Humans Isoenzymes - genetics Israel - epidemiology Leukemia, Myeloid, Acute - drug therapy Leukemia, Myeloid, Acute - epidemiology Leukemia, Myeloid, Acute - genetics Male Membrane Transport Proteins - genetics Middle Aged Multidrug Resistance-Associated Proteins - genetics NAT1/2 Neoplasm Proteins - genetics Pharmacogenetics Polymorphism, Genetic - genetics Predisposition Prognosis Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism
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Zusammenfassung:	Abstract Drug metabolism/disposition and transporter genes may influence predisposition or prognosis of AML (acute myeloid leukemia) patients. We analyzed polymorphisms in 3 transporters and 4 drug metabolism genes in 293 Israeli individuals (112 AML patients and 181 controls). We analyzed: ABCC3 (MRP3) C-211T ; ABCG2 ( BCRP ) C421A ; CNT1 ( SLC28A1 ) G565A and NAT1 , NAT2 , and GSTT1 and GSTM1 null alleles for influence on predisposition, as well as treatment response and survival. We found that the ABCC3 C-211T polymorphism and GSTM1 null genotype have adverse prognostic significance in AML. None of the other polymorphisms studied were found to influence either predisposition or prognosis in Israeli AML patients.
ISSN:	0145-2126 1873-5835
DOI:	10.1016/j.leukres.2007.10.011