DISEASE OVERVIEW: 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.
DIAGNOSIS: 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.
FRONTLINE THERAPY: 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.
SALVAGE THERAPY: 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.