Resistance of Leukemia Cells to 5-Azacytidine: Different Responses to the Same Induction Protocol

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F23%3A73621343" target="_blank" >RIV/61989592:15110/23:73621343 - isvavai.cz</a>
Result on the web
<a href="http://mdpi.com/2072-6694/15/11/3063" target="_blank" >http://mdpi.com/2072-6694/15/11/3063</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/cancers15113063" target="_blank" >10.3390/cancers15113063</a>

Result language
angličtina
Original language name
Resistance of Leukemia Cells to 5-Azacytidine: Different Responses to the Same Induction Protocol
Original language description
Three AML cell variants (M/A, M/A* from MOLM-13 and S/A from SKM-1) were established for resistance by the same protocol using 5-azacytidine (AZA) as a selection agent. These AZA-resistant variants differ in their responses to other cytosine nucleoside analogs, including 5-aza-2′-deoxycytidine (DAC), as well as in some molecular features. Differences in global DNA methylation, protein levels of DNA methyltransferases, and phosphorylation of histone H2AX were observed in response to AZA and DAC treatment in these cell variants. This could be due to changes in the expression of uridine-cytidine kinases 1 and 2 (UCK1 and UCK2) demonstrated in our cell variants. In the M/A variant that retained sensitivity to DAC, we detected a homozygous point mutation in UCK2 resulting in an amino acid substitution (L220R) that is likely responsible for AZA resistance. Cells administered AZA treatment can switch to de novo synthesis of pyrimidine nucleotides, which could be blocked by inhibition of dihydroorotate dehydrogenase by teriflunomide (TFN). This is shown by the synergistic effect of AZA and TFN in those variants that were cross-resistant to DAC and did not have a mutation in UCK2.
Czech name
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Czech description
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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
30204 - Oncology

Project
<a href="/en/project/EF18_053%2F0016919" target="_blank" >EF18_053/0016919: Support of mobility at Palacky University Olomouc II.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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