The Interface between BCR-ABL-Dependent and -Independent Resistance Signaling Pathways in Chronic Myeloid Leukemia

Autor: Nestal de Moraes, Gabriela, Souza, Paloma Silva, Costas, Fernanda Casal de Faria, Vasconcelos, Flavia Cunha, Reis, Flaviana Ruade Souza, Maia, Raquel Ciuvalschi
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Leukemia Research and Treatment.
ISSN: 2090-3219
DOI: 10.1155/2012/671702
Popis: 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.
Databáze: OpenAIRE