title: Tyrosine kinase inhibitors in acute and chronic leukemias.
abstract: BACKGROUND
  Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy. Targeted therapy with TKIs has continued to be an area of active research and development in the care of acute and chronic leukemia patients.
  
  
  METHODS
  This article reviews current approved and investigational TKI treatments for chronic myelogenous leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph + ALL) and acute myelogenous leukemia (AML).
  
  
  CONCLUSIONS
  There are now more potent BCR-ABL TKIs approved, which allow for additional options when determining front-line and second-line CML and Ph + ALL treatments. The T315I mutation is an ever-present challenge. Ponatinib, a pan BCR-ABL TKI, while still under investigation, is very hopeful with its ability to overcome T315I mutations in resistant CML and Ph + ALL patients. Because nilotinib and dasatinib have not been directly compared, at present we recommend selecting one or the other based on the side-effect profile, drug interactions, patient comorbidities, and mutational status. FLT-3 inhibition is of particular interest in AML patients with FLT-3 internal tandem duplication mutations; this type of targeted therapy continues to be studied.
authors.affiliation: The University of Texas, M. D. Anderson Cancer Center, Department of Leukemia, 1515 Holcombe Blvd, Box 428, Houston, TX 77030, USA.
authors.forename: Maro
authors.initials: M
authors.lastname: Ohanian
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
mesh_terms: D000208:Acute Disease; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002908:Chronic Disease; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases