title: New mechanisms of resistance in Philadelphia chromosome acute lymphoblastic leukemia.
abstract: The outcome for adults and children with Philadelphia chromosome acute lymphoblastic leukemia (ALL) has been improved dramatically with the use of tyrosine kinase inhibitors but relapse is an expected event in the majority of patients. We reviewed recent findings obtained from both gene-expression profiling analysis and single nucleotide polymorphism arrays and characterized by the identification of multiple novel genetic alterations targeting key cellular pathways, including lymphoid differentiation, cell cycle, tumor suppression, apoptosis and drug responsiveness. By gene-expression profiling analysis a new subtype known as 'BCR-ABL1-like' was identified, which includes 15-20% of all precursor B-ALL cases and is associated with an unfavorable outcome. By single nucleotide polymorphism array analysis, deletions of genes such as IKAROS, PAX5 and CDKN2A-CDKN2B were frequently identified. New therapeutic approaches are now available, such as dasatinib, nilotinib and bosutinib, and we highlight those that may be applicable to the treatment of adult BCR-ABL1-positive ALL.
authors.affiliation: Department of Hematology/Oncology L and A Seràgnoli, S. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy. giovanni.martinelli2@unibo.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iacobucci
authors.forename: Simona
authors.initials: S
authors.lastname: Soverini
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Daniela
authors.initials: D
authors.lastname: Cilloni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Pane
mesh_terms: D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors