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Towards unravelling the kinetics of an acute myeloid leukaemia model system under oxidative and starvation stress: a comparison between two- and three-dimensional cultures


A great challenge when conducting ex vivo studies of leukaemia is the construction of an appropriate experimental platform that would recapitulate the bone marrow (BM) environment. Such a 3D scaffold system has been previously developed in our group [1]. Additionally to the BM architectural characteristics, parameters such as oxygen and glucose concentration are crucial as their value could differ between patients as well as within the same patient at different stages of treatment, consequently affecting the resistance of leukaemia to chemotherapy. The effect of oxidative and glucose stress—at levels close to human physiologic ones—on the proliferation and metabolic evolution of an AML model system (K-562 cell line) in conventional 2D cultures as well as in 3D scaffolds were studied. We observed that the K-562 cell line can proliferate and remain alive for 2 weeks in medium with glucose close to physiological levels both in 20 and 5 % O2. We report interesting differences on the cellular response to the environmental, i.e., oxidative and/or nutritional stress stimuli in 2D and 3D. Higher adaptation to oxidative stress under non-starving conditions is observed in the 3D system. The glucose level in the medium has more impact on the cellular proliferation in the 3D compared to the 2D system. These differences can be of significant importance both when applying chemotherapy in vitro and also when constructing mathematical tools for optimisation of disease treatment.

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This work is supported by ERC-BioBlood (no. 340719), ERC-Mobile Project (no. 226462), by the EU 7th Framework Programme [MULTIMOD Project FP7/2007-2013, no. 238013] and by the Richard Thomas Leukaemia Research Fund. R. M. is further thankful for a Royal Academy of Engineering Research Fellowship.

Author information

Correspondence to Eirini G. Velliou.



Concentrations of nutrients in different growth media as detected by the NOVA bioprofiler

See Table 3.

Table 3 DMEM synthesis

Calibration curve of MTS vs live K-562 cells (2D system)

See Fig. 5.

Fig. 5

MTS standard curve of the K-562 cell line for 2D culture

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Velliou, E.G., Dos Santos, S.B., Papathanasiou, M.M. et al. Towards unravelling the kinetics of an acute myeloid leukaemia model system under oxidative and starvation stress: a comparison between two- and three-dimensional cultures. Bioprocess Biosyst Eng 38, 1589–1600 (2015). https://doi.org/10.1007/s00449-015-1401-z

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  • Acute myeloid leukaemia
  • Starvation stress
  • Oxidative stress
  • 3D scaffolds
  • K-562 cell line