METABOLOMIC PROFILING IDENTIFIES GLYCOLYSIS PATHWAY ASSOCIATION WITH ASPARAGINASE RESISTANCE IN ACUTE LYMPHOBLASTIC LEUKEMIA CELL LINES
DOI:
https://doi.org/10.61229/mpj.v1i1.2Keywords:
Metabolomics, Acute Lymphoblastic Leukemia, Asparaginase resistanceAbstract
early response to therapy has consistently shown independent prognostic significance in pediatric acute lymphoblastic leukemia (all) and can be attributed primarily to the intrinsic resistance/sensitivity of leukemic lymphoblasts to chemotherapy. in this study, our objective was to determine the metabolic profile after l-asparaginase (asnase) treatment of cell lines resistant and sensitive to this drug by nmr metabolomics. all cell lines nalm6, nalm21, reh and rs4;11 were cultured in rpmi 1640 medium plus 10% fbs, supplemented or not with asnase (0.8 iu/ml). after 24hs, nmr spectra of the culture medium were acquired and quantified. unsupervised pca analysis of the obtained metabolites concentrations showed that resistant cells culture medium are characterized by lower glucose and higher lactate levels. interestingly, inhibition of the glycolysis pathway synergistically increased sensitivity of the resistant cell lines to asnase (fsyn = 0.19 for nalm6 and fsyn = 0.50 for reh) but not of the sensitive one (fsyn = 1.11 for nalm21 and fsyn = 1.85 for rs4;11). in conclusion, this study shows a potential metabolomics approach for the identification not only of patients with possible resistance to treatment, but also of target molecules for the development of future therapeutic interventions.
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