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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-12-21
pubmed:abstractText
Drug resistance constitutes a considerable problem in the therapy of acute myeloid leukemia (AML). In order to identify genes which might be related to drug resistance, we retrospectively studied gene expression patterns in blast populations of 14 patients with de novo AML, focusing on known or potential resistance mechanisms against cytosine arabinoside and anthracyclines. Following induction and postremission chemotherapy, 7 patients achieved a complete remission (CR) for more than 1 year, while 7 patients showed blast persistence (BP) after induction and salvage chemotherapy. Gene expression analysis was performed using RNA extracted from archived guanidine extracts and Affymetrix HGU133A gene chips. We utilized the Gene Ontology category Biological Process to select genes implicated in DNA metabolism, nucleoside and nucleotide metabolism and transport, reactive oxygen species metabolism, apoptosis and response to drugs and identified 32 differentially expressed genes. From this functional perspective, we found differences between the CR and BP groups with regard to nucleotide metabolism (PBEF1, G6PD; p = 0.048), apoptosis (TNFAIP3, TNFAIP8, MPO, BCL2A1, BAX, SON, BNIP3L; p = 0.039) and reactive oxygen species metabolism (SOD2, KIAA0179; p = 0.048). However, the attempt to construct a predictive model of chemoresistance failed. BP samples had a 2-fold higher expression of CD34 than CR samples. Thus, our findings are in line with reports describing differences in apoptosis resistance between CD34+ and CD34- blast populations. Taken together, our results suggest that drug resistance in AML is a heterogenous phenomenon that might be better defined by means of disturbed biological processes than by focusing on the alteration of the expression of distinct genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0001-5792
pubmed:author
pubmed:copyrightInfo
2007 S. Karger AG, Basel
pubmed:issnType
Print
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8-15
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17095854-Acute Disease, pubmed-meshheading:17095854-Adolescent, pubmed-meshheading:17095854-Adult, pubmed-meshheading:17095854-Antigens, CD34, pubmed-meshheading:17095854-Antineoplastic Agents, pubmed-meshheading:17095854-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:17095854-Apoptosis, pubmed-meshheading:17095854-Drug Resistance, Neoplasm, pubmed-meshheading:17095854-Female, pubmed-meshheading:17095854-Gene Expression Profiling, pubmed-meshheading:17095854-Humans, pubmed-meshheading:17095854-Leukemia, Myeloid, pubmed-meshheading:17095854-Male, pubmed-meshheading:17095854-Middle Aged, pubmed-meshheading:17095854-Neoplasm Proteins, pubmed-meshheading:17095854-Neoplastic Stem Cells, pubmed-meshheading:17095854-Nucleosides, pubmed-meshheading:17095854-Nucleotides, pubmed-meshheading:17095854-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:17095854-Oxidative Stress, pubmed-meshheading:17095854-RNA, Neoplasm, pubmed-meshheading:17095854-Remission Induction, pubmed-meshheading:17095854-Salvage Therapy, pubmed-meshheading:17095854-Superoxides, pubmed-meshheading:17095854-Treatment Outcome
pubmed:year
2007
pubmed:articleTitle
Differential expression of drug-resistance-related genes between sensitive and resistant blasts in acute myeloid leukemia.
pubmed:affiliation
Department of Internal Medicine (Cancer Research), University of Essen, Medical School, Essen, Germany. lewin.eisele@uni-essen.de
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't