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  • The survival of patients with chronic myeloid leukemia (CML) has improved significantly since the advent of tyrosine kinase inhibitor (TKI) therapy. With the availability of TKI and proper management, the expected survival of patients with chronic phase CML (CML-CP) is approaching that of the general population.

  • Any of the four TKIs approved for frontline therapy of CML-CP may be selected. These include imatinib, dasatinib, nilotinib, and bosutinib. Second-generation TKIs are superior to imatinib in achieving faster and deeper responses compared with imatinib, but survival is similar because of the availability of effective TKI salvage therapies.

  • Factors considered in choosing TKI therapy in the frontline setting include patient age, comorbidities, adverse events profile, and disease risk score, as well as the TKI-associated schedule of administration and cost. Kinase domain mutation profile plays no role in selecting an initial TKI but becomes relevant in relapse.

  • Most TKIs are reasonably well tolerated with close observation and supportive care. However, each TKI therapy has a distinct toxicity profile that should be considered when deciding on therapy.

  • Second- and third-generation TKIs have not been compared head to head. Mutational analysis is required after failure of imatinib or second-generation TKIs, or after progression to accelerated phase CML (CML-AP) or blastic phase (CML-BP). Baseline mutational analysis are not recommended in newly diagnosed CML-CP because it does not help predict treatment outcome.

  • Allogeneic stem cell transplant should be considered in patients who progress from CML-CP to CML-AP/CML-BP after TKI therapy failure and who fail second- or third-generation TKI while still in CML-CP.


Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pluripotent hematopoietic stem cells. The Philadelphia (Ph) chromosome results from a reciprocal translocation between chromosomes 9 and 22 and constitutes the cytogenetic hallmark of CML. A critical milestone in CML research was the demonstration that this translocation involved the ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1) gene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22 and resulted in the formation of the chimeric BCR-ABL1 fusion transcript that encodes the constitutively active BCR-ABL1 tyrosine kinase.1 This in turn is responsible for cell growth and replication through downstream signaling pathways.2–8 The discovery that BCR-ABL1 plays a pivotal role in the pathogenesis of CML set the stage for the development of therapeutic strategies aimed specifically at inhibiting this kinase and its downstream signals. Herein, we summarize the current knowledge regarding the molecular biology of CML and the treatment modalities, including novel BCR-ABL1 tyrosine kinase inhibitors (TKIs).


CML has an incidence of 1 to 2 cases per 100,000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.9 The median age of onset of CML is 60 to 65 years, and the incidence increases with age. There are no known hereditary, geographic, familial, or ethnic associations. There are no known causal etiologies, although an ...

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