title: Current status of agents active against the T315I chronic myeloid leukemia phenotype.
abstract: BACKGROUND
  T315I is a genetic mutation of the Bcr-Abl tyrosine kinase, the pathogenetic abnormality in chronic myeloid leukemia (CML). It accounts for 10 ? 15% of clinically relevant CML mutations. Licensed tyrosine kinase inhibitors are ineffective against this mutation and its development reduces life expectancy of CML in chronic phase from 10 years to just 22 months. Extensive work is ongoing to establish the most effective therapy to overcome this mutation, including the development of novel specific agents and also re-examination of established therapies.
  
  
  METHODS
  This review examines the agents in development, dividing them into Bcr-Abl-dependant and -independent groups. It looks at the progress of this research, updating the reader on the status of agents previously reported and introducing emerging therapeutic possibilities only recently announced.
  
  
  CONCLUSIONS
  Development of the T315I mutation is a devastating event for some patients with CML. There are potential therapeutic agents at all stages of the drug development cycle to target this patient subpopulation. Clinical activity has been demonstrated and a number of agents are on the cusp of being licensed and available for use.
authors.affiliation: HRB Clinical Research Facility, National University of Ireland Galway and Trinity College Dublin, Ireland.
authors.forename: Aine Carol
authors.initials: AC
authors.lastname: Burke
authors.forename: Ronan T
authors.initials: RT
authors.lastname: Swords
authors.forename: Kevin
authors.initials: K
authors.lastname: Kelly
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic; D055808:Drug Discovery / Q000379:methods*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl