The impact of fluctuations of environmental parameters
such as oxygen and starvation on the evolution of leukaemia
is analysed in the current review. These fluctuations may occur
within a specific patient (in different organs) or across patients
(individual cases of hypoglycaemia and hyperglycaemia). They
can be experienced as stress stimuli by the cancerous population,
leading to an alteration of cellular growth kinetics, metabolism
and further resistance to chemotherapy. Therefore, it is of high
importance to elucidate key mechanisms that affect the evolution
of leukaemia under stress. Potential stress response mechanisms
are discussed in this review. Moreover, appropriate cell biomarker
candidates related to the environmental stress response and/or
further resistance to chemotherapy are proposed. Quantification
of these biomarkers can enable the combination of macroscopic kinetics
with microscopic information, which is specific to individual
patients and leads to the construction of detailed mathematical
models for the optimisation of chemotherapy. Due to their nature,
these models will be more accurate and precise (in comparison
to available macroscopic/black box models) in the prediction of
responses of individual patients to treatment, as they will incorporate
microscopic genetic and/or metabolic information which is
patient-specific.peer-reviewe
