title: The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia.
abstract: Chronic myeloid leukemia (CML) is a clonal hematopoietic disorder characterized by the presence of the Philadelphia chromosome which resulted from the reciprocal translocation between chromosomes 9 and 22. The pathogenesis of CML involves the constitutive activation of the BCR-ABL tyrosine kinase, which governs malignant disease by activating multiple signal transduction pathways. The BCR-ABL kinase inhibitor, imatinib, is the front-line treatment for CML, but the emergence of imatinib resistance and other tyrosine kinase inhibitors (TKIs) has called attention for additional resistance mechanisms and has led to the search for alternative drug treatments. In this paper, we discuss our current understanding of mechanisms, related or unrelated to BCR-ABL, which have been shown to account for chemoresistance and treatment failure. We focus on the potential role of the influx and efflux transporters, the inhibitor of apoptosis proteins, and transcription factor-mediated signals as feasible molecular targets to overcome the development of TKIs resistance in CML.
authors.affiliation: Laboratório de Hemato-Oncologia Celular e Molecular, Programa de Pesquisa em Hemato-Oncologia Molecular, Instituto Nacional de Câncer (INCA), Praça da Cruz Vermelha 23, 6° andar, Centro, 20230-130 Rio de Janeiro, RJ, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Nestal de Moraes
authors.forename: Paloma Silva
authors.initials: PS
authors.lastname: Souza
authors.forename: Fernanda Casal de Faria
authors.initials: FC
authors.lastname: Costas
authors.forename: Flavia Cunha
authors.initials: FC
authors.lastname: Vasconcelos
authors.forename: Flaviana Ruade Souza
authors.initials: FR
authors.lastname: Reis
authors.forename: Raquel Ciuvalschi
authors.initials: RC
authors.lastname: Maia