title: Molecular biology of bcr-abl1-positive chronic myeloid leukemia.
abstract: Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. aquintas@mdanderson.org
authors.forename: Alfonso
authors.initials: A
authors.lastname: Quintás-Cardama
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000818:Animals; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000503:physiopathology*; D008967:Molecular Biology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D016044:Fusion Proteins, bcr-abl