Up-regulation of asparagine synthetase expression is not linked to the clinical response L-asparaginase in pediatric acute lymphoblastic leukemia.

@article{Appel2006UpregulationOA,
  title={Up-regulation of asparagine synthetase expression is not linked to the clinical response L-asparaginase in pediatric acute lymphoblastic leukemia.},
  author={Inge M. Appel and Monique L. Den Boer and Jules P. P. Meijerink and Anjo J. P. Veerman and Nathalie Reniers and Rob Pieters},
  journal={Blood},
  year={2006},
  volume={107 11},
  pages={
          4244-9
        }
}
L-asparaginase (L-Asp) is an effective drug for treatment of children with acute lymphoblastic leukemia (ALL). The effectiveness is generally thought to result from a rapid depletion of asparagine in serum and cells. Asparagine synthetase (AS) opposes the action of L-Asp by resynthesis of asparagine. In vitro, resistance to L-Asp has been associated with up-regulation of AS mRNA expression. We monitored AS mRNA levels in leukemic cells before and during 5 days after intravenous administration… 
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Expression of asparagine synthetase predicts in vitro response to l-asparaginase in canine lymphoid cell lines
TLDR
Using canine lymphoid cell lines, it is found that L-asp sensitivity is strongly negatively correlated with the level of methylation of the asparagine synthetase (ASNS) promoter, and ASNS methylation and expression is not predictive of overall survival or progression-free survival in canine lymphoma patients treated with l-asp.
Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro
TLDR
Functional analyses indicated that AsnS did not affect the proliferation and apoptosis of ENKTL cells in the absence of asparaginase, and a different therapeutic strategy for patients with a different level of AsNS expression was suggested.
Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study
TLDR
No changes in apoptotic parameters or in intracellular levels of twenty amino acids in leukemic cells could be measured, in contradiction to the changes found after in vitro exposure, which may be explained by the rapid removal of apoptotic cells from the circulation in vivo.
Asparagine Synthetase Expression and Phase I Study With L-Asparaginase Encapsulated in Red Blood Cells in Patients With Pancreatic Adenocarcinoma
TLDR
In the phase I trial, ERY-ASP was well tolerated by patients with metastatic PAC and should be evaluated in further clinical studies in metastaticPAC.
Update on the Use of l-Asparaginase in Infants and Adolescent Patients with Acute Lymphoblastic Leukemia
TLDR
An overview on L-ASP data is presented and cellular mechanisms underlying resistance and alternative therapies for the use of asparaginase in childhood ALL treatment are focused on.
Tolerability and Efficacy of L-Asparaginase Therapy in Pediatric Patients With Acute Lymphoblastic Leukemia
TLDR
Although L-ASNase is well-tolerated in most patients and causes little myelosuppression, significant toxicities occur in up to 30% of patients and Hypersensitivity is the most common toxicity of L- ASNase therapy and limits the further use of the drug.
Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines.
Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase.
TLDR
Results provide what the authors believe to be a new basis for understanding asparaginase resistance in ALL and indicate that MSC niches in the bone marrow can form a safe haven for leukemic cells.
A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase.
TLDR
It is reported that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase, a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia.
Expression levels of ASNS in mesenchymal stromal cells in childhood acute lymphoblastic leukemia
TLDR
The results indicate that MSC ASNS mRNA expression is upregulated in ALL samples compared to controls, and it is observed that the values of the ASNS RNA of MSC seem to reach a peak at diagnosis, and tend to decline with treatment.
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References

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TLDR
The sensitivity of t(12;21)(+) childhood ALL to L-Asp is not associated with the expression level of the AS gene, contradicting the general thought that leukemic cells specifically lack AS compared with normal bone marrow and blood cells.
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TLDR
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