title: Chronic myeloid leukemia: 2012 update on diagnosis, monitoring, and management.
abstract: BACKGROUND
  Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of one-two 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 2nd generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined.
  For patients who fail standard-dose imatinib therapy, imatinib dose escalation is a second-line option. Alternative second-line options include 2nd generation TKIs. Although both are potent and specific BCR-ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR-ABL mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs and are candidate for clinical trials. Allogeneic transplantation remains an important therapeutic option for CML-CP harboring the T315I mutation, patients who fail 2nd generation TKIs, and for all patients in advanced phase disease.
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ejabbour@mdanderson.org
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D000069439:Dasatinib; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016879:Salvage Therapy; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D013844:Thiazoles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib; D000069439:Dasatinib