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Decreased survival ...
Decreased survival in normal karyotype AML with single-nucleotide polymorphisms in genes encoding the AraC metabolizing enzymes cytidine deaminase and 5'-nucleotidase
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- Jakobsen Falk, Ingrid (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet
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- Fyrberg, Anna (author)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet
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- Paul, Esbjörn (author)
- Karolinska Institutet, Stockholm, Sweden
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- Nahi, Hareth (author)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Hermanson, Monica (author)
- Uppsala universitet,Medicinsk genetik
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- Rosenquist, Richard Brandell (author)
- Uppsala universitet,Hematologi och immunologi
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- Höglund, Martin (author)
- Uppsala universitet,Hematologi
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- Palmqvist, Lars, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,University of Gothenburg, Sweden
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- Stockelberg, Dick, 1950 (author)
- Sahlgrenska University Hospital, Gothenburg, Sweden
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- Wei, Yuan, 1978 (author)
- Sahlgrenska University Hospital, Gothenburg, Sweden
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- Gréen, Henrik (author)
- KTH,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Genteknologi,Science for Life Laboratory, SciLifeLab
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- Lotfi, Kourosh (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för läkemedelsforskning,Hälsouniversitetet,Klinisk farmakologi
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(creator_code:org_t)
- 2013-09-09
- 2013
- English.
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In: American Journal of Hematology. - : John Wiley & Sons. - 0361-8609 .- 1096-8652. ; 88:12, s. 1001-1006
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Abstract
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- De novo acute myeloid leukemia with normal karyotype (NK-AML) comprises a large group of patients with no common cytogenetic alterations and with a large variation in treatment response. Single-nucleotide polymorphisms (SNPs) in genes related to the metabolism of the nucleoside analogue AraC, the backbone in AML treatment, might affect drug sensitivity and treatment outcome. Therefore, SNPs may serve as prognostic biomarkers aiding clinicians in individualized treatment decisions, with the aim of improving patient outcomes. We analyzed polymorphisms in genes encoding cytidine deaminase (CDA 79A>C rs2072671 and −451C>T rs532545), 5′-nucleotidase (cN-II 7A>G rs10883841), and deoxycytidine kinase (DCK 3′UTR 948T>C rs4643786) in 205 de novo NK-AML patients. In FLT3-internal tandem duplication (ITD)-positive patients, the CDA 79C/C and −451T/T genotypes were associated with shorter overall survival compared to other genotypes (5 vs. 24 months, P < 0.001 and 5 vs. 23 months, P = 0.015, respectively), and this was most pronounced in FLT3-ITD-positive/NPM1-positive patients. We observed altered in vitro sensitivity to topoisomerase inhibitory drugs, but not to nucleoside analogues, and a decrease in global DNA methylation in cells carrying both CDA variant alleles. A shorter survival was also observed for the cN-II variant allele, but only in FLT3-ITD-negative patients (25 vs. 31 months, P = 0.075). Our results indicate that polymorphisms in genes related to nucleoside analog drug metabolism may serve as prognostic markers in de novo NK-AML
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- MEDICINE
- MEDICIN
- Nothing to report
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Jakobsen Falk, I ...
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Fyrberg, Anna
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Paul, Esbjörn
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Nahi, Hareth
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Hermanson, Monic ...
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Rosenquist, Rich ...
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show more...
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Höglund, Martin
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Palmqvist, Lars, ...
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Stockelberg, Dic ...
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Wei, Yuan, 1978
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Gréen, Henrik
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Lotfi, Kourosh
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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American Journal ...
- By the university
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Linköping University
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Royal Institute of Technology
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University of Gothenburg
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Karolinska Institutet
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Uppsala University