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BERNARDO SPAGNOLO

Stochastic modelling of imatinib-treated leukemic cell dynamics

  • Authors: Pizzolato, N; Valenti, D; Persano Adorno, D; Spagnolo, B
  • Publication year: 2007
  • Type: Altro
  • Key words: Leukemic cell dynamics; noise
  • OA Link: http://hdl.handle.net/10447/38120

Abstract

Chronic Myeloid Leukemia (CML) is a slowly progressing cancer that makes the body produce too many cancerous myeloid white blood cells. The molecular characteristics of CML is the presence of a Philadelphia (Ph) chromosome, created by a reciprocal translocation of chromosomes 9 and 22 which generates the fusion oncogene BCR-ABL. The introduction of the ABL tyrosine kinase inhibitor imatinib (Gleevec) for the treatment of CML represents the first example of a successful targeted therapy. Despite its striking efficacy, however, the developement of resistance to imatinib is observed in a proportion of patients, expecially those with advanced-stage CML. In the present work, the dynamics of the cancer progression is modelled by considering the stochastic evolution a population ofN reproducing cells which can experience genetic mutations. Several scenarios of the evolutionary dynamics of imatinibtreated leukaemic cells are described as a consequence of the efficacy of the different modelled therapies. The development of resistance is also investigated.