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Chronic Myelogenous Leukemia: Learning Objectives

 

Medical Importance

Chronic myelogenous leukemia (CML) accounts for 15-20 percent of all leukemias and was the first malignancy in which a specific chromosomal abnormality (the Philadelphia chromosome) was identified. Characterization of the molecular consequences of this chromosomal abnormality identified an activated oncogene, Bcr-Abl, as the cause of this disease. A drug designed to inhibit Bcr-Abl signaling presents a model for the understanding and treatment of a disease based on a specific molecular defect. 

Objectives

  1. Diagram the chromosomal translocation that generates the Philadelphia chromosome, identify the genes involved and the protein created by this translocation.
  2. Describe how the bcr-abl fusion protein causes leukemia and provides a target for effective therapy in CML.
  3. Describe the presenting features of CML, including age at presentation, the most common symptoms, one physical exam finding, and a typical CBC.
  4. Describe the typical findings on the blood smear in patients with CML, emphasizing the number and types of leukocytes seen in the blood.
  5. For a patient with chronic phase CML, compare and contrast treatment with imatinib and other tyrosine kinase inhibitors versus allogeneic stem cell transplantation in terms of goals of treatment, side effects, and long-term outcome.