Novel therapeutic targets in chronic myeloid leukaemia through a discrete time discrete Markov chain model of BCR-ABL1 interactions

Abstract

Chronic Myeloid Leukaemia (CML) is a blood-derived proliferative disorder, which is highly associated to a translocation of chromosomes 9 and 22 or the creation of Philadelphia chromosome Ph(+) cases, inducing the synthesis of a chimeric fusion protein, namely BCR-ABL1 (Breakpoint Cluster Region-Abelson 1 chimeric protein), which is known for driving the pathophysiology of the disease, however variants of CML are also recognized as CML Ph(-), these nonetheless account for a small percentage of the overall CML patients; posing thus the question whether BCR-ABL1 fusion protein is required for the whole of the pathophysiology of CML. Hereof, through a stochastic description, a discrete time discrete Markov chain depicts the various protein-protein interactions of BCR-ABL1 to better understand signalling pathways and time-dependent evolution of these pathways, as well as to provide prospective therapeutic protein targets to improve both the specificity of the treatment and the life-expectancy of the patients.

Tasks

Reproductions