title: Which tyrosine-kinase inhibitor to use first in chronic phase chronic myelogenous leukemia?
abstract: BACKGROUND
  Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder distinctly characterized by the presence of the Philadelphia chromosome, which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22)]. The resulting translocation leads to the development of the BCR-ABL1 oncogene, a constitutively active fusion protein, which leads to uncontrolled cell proliferation and reduced apoptosis and has a clear association with driving the malignant activity of CML cells.
  
  
  METHODS
  Given that the BCR-ABL1 oncogene is a known key cause of CML, it has led to the development of numerous small molecule tyrosine-kinase inhibitors (TKIs), which target the specific oncogene mutation in CML. Presently, there are three FDA-approved TKI agents, imatinib, dasatinib and nilotinib, for the treatment of frontline CML. Herein, we review the frontline options for the management of patients with CML and how to best choose these agents.
  
  
  CONCLUSIONS
  Imatinib, dasatinib and nilotinib are all effective at yielding hematological, molecular and cytogenetic responses in patients with newly diagnosed CML. Frontline therapy may depend on physician experience, patient age and ability to tolerate therapy, and with the lack of data comparing all three agents alongside each other, imatinib, dasatinib, or nilotinib may all be suitable frontline choices.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Division of Pharmacy and Department of Leukemia , 1515 Holcombe BLVD, unit 377, Houston, TX 77030 , USA.
authors.forename: Morgan L
authors.initials: ML
authors.lastname: Mace
authors.forename: Jenny
authors.initials: J
authors.lastname: Dahl
authors.forename: Elias J
authors.initials: EJ
authors.lastname: Jabbour
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D000069439:Dasatinib; D019008:Drug Resistance, Neoplasm; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib
keywords: chronic myeloid leukemia; dasatinib; imatinib; nilotinib; tyrosine-kinase inhibitors