title: [Is AP24534 (Ponatinib) the next treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia?].
abstract: Distinct clinicopathologic acute lymphoblastic leukemia (ALL) entities have been identified, resulting in the adoption of risk-oriented treatment approaches. In Philadelphia chromosome-positive (Ph(+)) ALL, the optimal treatment requires the addition of BCR-ABL tyrosine kinase inhibitors, as imatinib. However, the outcome remains poor in absence of allogeneic stem cell transplantation, and novel agents are desperately required. Resistance attributable to kinase domain mutations can lead to relapse despite the development of second-generation compounds, including dasatinib and nilotinib. Despite these therapeutic options, the cross-resistant BCR-ABL (T315I) mutation remains a major clinical challenge. The first evaluations of AP24534 present this drug as a potent multi-targeted kinase inhibitor active against T315I and all other BCR-ABL mutants. AP24534 could be the next treatment of choice in hematological malignancies with Philadelphia-positive chromosome, particularly Ph(+) ALL known for its frequent occurrence of T315I mutation.
authors.affiliation: Hôpital Édouard-Herriot, Hématologie, 5, place d’Arsonval, 69437 Lyon, France. xavier.thomas@chu-lyon.fr
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011724:Pyridazines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011724:Pyridazines; C545373:ponatinib; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl