title: Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management.
abstract: BACKGROUND
  Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults, and accounts for ∼15% of newly diagnosed cases of leukemia in adults.
  
  
  METHODS
  CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL fusion oncogene, which in turn translates into a Bcr-Abl oncoprotein.
  Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib have been approved by the US Food and Drug Administration for the first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with second generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined.
  For patients who fail frontline therapy, second-line options include second and third generation TKIs. Although second and third generation TKIs are potent and specific BCR-ABL TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as patients comorbidities, disease stage, and BCR-ABL mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic transplantation remains an important therapeutic option for CML-CP who have failed at least 2 TKIs, and for all patients in advanced phase disease.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000628:therapy*