Figure 2

Representative outputs of simulating the long-term survival of leukemic T-LGL cells. (a). Inhibition of AICD by constitutive overexpression of MCL1 and sFas. Chronic antigen stimulation will induce the depletion of reactive CTL through AICD, as suggested by the asymptotic increase to 1 of apoptosis percentage in the output "Normal-Apop". Constitutive overexpression of MCL1 or sFas alone does not rescue reactive CTL from AICD, as suggested by the output "MCL1-Apop" and "sFas-Apop". However, when simulating the simultaneous overexpression of MCL1 and sFas, resistance to AICD was achieved, see output "LGL-like-Apop", as observed in leukemic T-LGL cells. (b). Additional characterization of the effect of simultaneous overexpression of MCL1 and sFas. In addition to the inhibition of AICD, simulations under conditions mimicking the constitutive overexpression of MCL1 and sFas also reproduced the known deregulated signaling pathway components in leukemic T-LGL cells, such as constitutively overexpressed FasL ("LGL-like-FasL") and constitutively activated Ras ("LGL-like-Ras"), were reproduced compared to simulations mimicking normal CTL activation ("Normal-FasL" and "Normal-Ras").