title: Abl: the prototype of oncogenic fusion proteins.
abstract: Since it was first recognized, chronic myeloid leukemia (CML) has always represented a unique model to understand the molecular mechanisms underlying the onset and progression of a leukemic process. CML was the first recognized form of cancer to have a strong association with a recurrent chromosomal abnormality, the t(9;22) translocation, which generates the so-called Philadelphia (Ph)-chromosome. Twenty years later, this abnormality was shown to cover a specific molecular defect, a hybrid BCR-ABL gene, strongly implicated in the pathogenesis of the disease through the production of a protein with a constitutive tyrosine-kinase activity. Although we still lack a complete definition of all the transformation pathways activated by Bcr-Abl, the recent introduction into clinical practice of tyrosine kinase inhibitor represents a major breakthrough to the management of CML and, furthermore, promises to usher in molecularly targeted therapy for other types of leukemia, lymphoma and cancer.
authors.affiliation: Dept. of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Gonzole 10, 10043 Orbassano-Torino, Italy. giuseppe.saglio@unito.it
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: D
authors.initials: D
authors.lastname: Cilloni
mesh_terms: D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D005091:Exons; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D010677:Philadelphia Chromosome; D017434:Protein Structure, Tertiary; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014178:Translocation, Genetic
chemical_list: D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl