{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:32:43Z","timestamp":1791232363889,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T00:00:00Z","timestamp":1350950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Disease overview:<\/jats:title><jats:p>Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm with an incidence of one\u2013two cases per 100,000 adults and accounts for \u223c15% of newly diagnosed cases of leukemia in adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Diagnosis:<\/jats:title><jats:p>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\u2010ABL fusion oncogene, which in turn translates into a Bcr\u2010Abl oncoprotein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Frontline therapy:<\/jats:title><jats:p>Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib, have been approved by the US Food and Drug Administration for the first\u2010line treatment of patients with newly diagnosed CML in chronic phase (CML\u2010CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long\u2010term survival remains to be determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Salvage therapy:<\/jats:title><jats:p>For patients who fail standard\u2010dose imatinib therapy, imatinib dose escalation is a second\u2010line option. Alternative second\u2010line options include 2nd generation TKIs. Although both are potent and specific BCR\u2010ABL TKIs, dasatinib and nilotinib exhibit unique pharmacological profiles and response patterns relative to different patient characteristics, such as disease stage and BCR\u2010ABL mutational status. Patients who develop the T315I \u201cgatekeeper\u201d mutation display resistance to all currently available TKIs and are candidate for clinical trials. Allogeneic transplantation remains an important therapeutic option for CML\u2010CP harboring the T315I mutation, patients who fail 2nd generation TKIs, and for all patients in advanced phase disease. Am. J. 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