Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response of chronic myeloid leukemia patients to imatinib treatment
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10362332" target="_blank" >RIV/00216208:11110/17:10362332 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11150/17:10362332 RIV/00216208:11310/17:10362332 RIV/00179906:_____/17:10362332 RIV/00023736:_____/17:00011752
Result on the web
<a href="http://dx.doi.org/10.1186/s13046-017-0523-3" target="_blank" >http://dx.doi.org/10.1186/s13046-017-0523-3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s13046-017-0523-3" target="_blank" >10.1186/s13046-017-0523-3</a>
Alternative languages
Result language
angličtina
Original language name
Genotypes of SLC22A4 and SLC22A5 regulatory loci are predictive of the response of chronic myeloid leukemia patients to imatinib treatment
Original language description
Background: Through high-throughput next-generation sequencing of promoters of solute carrier and ATP-binding cassette genes, which encode drug transporters, we aimed to identify SNPs associated with the response to imatinib administered for first-line treatment of patients with chronic myeloid leukemia. Methods: In silico analysis using publicly available databases was done to select the SLC and ABC genes and their promoters for the next-generation sequencing. SNPs associated with the imatinib response were identified using Fisher's exact probability tests and subjected to the linkage disequilibrium analyses with regulatory loci of concerned genes. We analyzed cumulative achievement of major molecular response and probability of event free survival in relation to identified SNP genotypes in 129 CML patients and performed multivariate analysis for determination of genotypes as independent predictors of outcome. Gene expression analysis of eight cell lines naturally carrying different genotypes was performed to outline an impact of genotypes on the gene expression. Results: We observed significant differences in the frequencies of the rs460089-GC and rs460089-GG (SLC22A4) genotypes among rs2631365-TC (SLC22A5) genotype carriers that were associated with optimal and non-optimal responses, respectively. Loci rs460089 and rs2631365 were in highly significant linkage disequilibrium with 12 regulatory loci in introns of SLC22A4 and SLC22A5 encoding imatinib transporters. Genotype association analysis with the response to imatinib indicated that rs460089-GC carriers had a significantly higher probability of achieving a stable major molecular response (BCR-ABL1 transcript level below or equal to 0.1% in the international scale). In contrast, the rs460089-GG represented a risk factor for imatinib failure, which was significantly higher in rs460089-GG_rs2631365-TC carriers.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/NT13899" target="_blank" >NT13899: THE NEXT GENERATION SEQUENCING AS A TOOL OF PERSONAL MEDICINE IN PATIENTS WITH MYELODYSPLASTIC SYNDROME AND CHRONIC MYELOID LEUKEMIA.</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Experimental and Clinical Cancer Research
ISSN
1756-9966
e-ISSN
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Volume of the periodical
36
Issue of the periodical within the volume
April
Country of publishing house
IT - ITALY
Number of pages
17
Pages from-to
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UT code for WoS article
000399769800001
EID of the result in the Scopus database
2-s2.0-85018495486