Synergistic Cytotoxic Effect of L-Asparaginase Combined with Decitabine as a Demethylating Agent in Pediatric T-ALL, with Specific Epigenetic Signature
Joint Authors
Pession, Andrea
Astolfi, Annalisa
Bertuccio, Salvatore N.
Melchionda, Fraia
Serravalle, Salvatore
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-6, 6 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-11-27
Country of Publication
Egypt
No. of Pages
6
Main Subjects
Abstract EN
T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy.
Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients’ outcome and response to chemotherapy.
Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation.
Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment.
Hence we treated different T-ALL cell lines with L-asparaginase and correlated different responses to the treatment with ASNS expression.
Then we demonstrated that the ASNS expression was dependent on the methylation status of the promoter.
Finally we showed that, despite the demethylating effect on the ASNS gene expression, the combined treatment with the demethylating agent Decitabine could synergistically improve the L-asparaginase sensitivity in those T-ALL cell lines characterized by hypermethylation of the ASNS gene.
In conclusion, this preclinical study identified an unexpected synergistic activity of L-asparaginase and Decitabine in the subgroup of T-ALL with low ASNS expression due to hypermethylation of the ASNS promoter, while it did not restore sensitivity in the resistant cell lines characterized by higher ASNS expression.
American Psychological Association (APA)
Serravalle, Salvatore& Bertuccio, Salvatore N.& Astolfi, Annalisa& Melchionda, Fraia& Pession, Andrea. 2016. Synergistic Cytotoxic Effect of L-Asparaginase Combined with Decitabine as a Demethylating Agent in Pediatric T-ALL, with Specific Epigenetic Signature. BioMed Research International،Vol. 2016, no. 2016, pp.1-6.
https://search.emarefa.net/detail/BIM-1097011
Modern Language Association (MLA)
Serravalle, Salvatore…[et al.]. Synergistic Cytotoxic Effect of L-Asparaginase Combined with Decitabine as a Demethylating Agent in Pediatric T-ALL, with Specific Epigenetic Signature. BioMed Research International No. 2016 (2016), pp.1-6.
https://search.emarefa.net/detail/BIM-1097011
American Medical Association (AMA)
Serravalle, Salvatore& Bertuccio, Salvatore N.& Astolfi, Annalisa& Melchionda, Fraia& Pession, Andrea. Synergistic Cytotoxic Effect of L-Asparaginase Combined with Decitabine as a Demethylating Agent in Pediatric T-ALL, with Specific Epigenetic Signature. BioMed Research International. 2016. Vol. 2016, no. 2016, pp.1-6.
https://search.emarefa.net/detail/BIM-1097011
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1097011