title: Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring.
abstract: BACKGROUND
  Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100,000 adults. It accounts for approximately 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 gene (ABL1) 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-ABL1 fusion oncogene, which in turn translates into a BCR-ABL oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib are approved by the United States Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second-line options include second and third generation TKIs. Although second and third generation TKIs are potent and selective TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR-ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP who have failed at least two 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.affiliation: Department of Leukemia, the University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D016903:Drug Monitoring / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases