About: Mechanism of sensitivity and resistance to L-Asparaginase in leukemic cells     Goto   Sponge   NotDistinct   Permalink

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  • Childhood acute lymphoblastic leukaemia is treated using combined chemotherapy involving L-asparaginase. The cytotoxic effect of L-asparaginase rests on its ability to deplete extracellular asparagine. Leukaemic cells are very sensitive to the depletion of exogenous asparagine, probably due to the reduced activity of asparagine synthetase. Although many patients reach total remission, relapse and resistance to therapy remain a problem. The existing studies show that the mechanism of the development of resistance to L-asparaginase is independent on the expression of the gene for asparagine synthetase. High throughput methods, such as MicroArray, protein bead and CGH array, will enable us to identify new genes and pathways involved in the development of resistance. Characterisation of new genes might clarify the processes resulting in the development of the resistance and to a possible stratification of patients for the purposes of therapy. (en)
  • Akutní lymfoblastická leukémie u dětí je léčena kombinovanou chemoterapií, která zahrnuje enzym L-Asparaginázu. Cytotoxický efekt L-Asparaginázy spočívá ve schopnosti depletovat extracelulární asparagin. Leukemické buňky jsou na depleci exogenního asparaginu velmi citlivé pravděpodobně proto, že mají sníženou aktivitu enzymu asparagin syntetázy, která tyto aminokyseliny syntetizuje. Ačkoliv je procento pacientů dosahujících kompletní remise vysoké, relapsy a s nimi související rezistence na terapii zůstávají stále závažným problémem. Dosavadní studie ukazují, že mechanizmus vzniku rezistence na L-Asparaginázu je nezávislý na expresi genu pro asparagin syntetázu. High-throughput metody (microarray, protein bead array a CGH array) nám umožní identifikovat nové geny a také odhalit dráhy, které se účastní vzniku rezistence. Charakterizace nových genů by mohla vést k objasnění procesů vedoucích ke vzniku rezistence na toto chemoterapeutikum a k potenciální stratifikaci pacientů v rámci terapie.
Title
  • Mechanism of sensitivity and resistance to L-Asparaginase in leukemic cells (en)
  • Mechanismy citlivosti a resistence leukemických buněk na L-Asparaginázu
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  • NT12429
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  • acute lymphoblastic leukemia; L-Asparaginase; resistence; therapeutical protocol; expression profiling; cytometry bead assay; CGH array (en)
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  • acute lymphoblastic leukemia
  • expression profiling
  • resistence
  • L-Asparaginase
  • cytometry bead assay
  • therapeutical protocol
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