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
- Diagram the chromosomal translocation
that generates the Philadelphia chromosome, identify the genes involved
and the protein created by this translocation.
- Describe how the bcr-abl fusion protein causes leukemia and provides a target for effective therapy in CML.
- Describe
the presenting features of CML, including age at presentation, the most
common symptoms, one physical exam finding, and a typical CBC.
- Describe
the typical findings on the blood smear in patients with CML,
emphasizing the number and types of leukocytes seen in the blood.
- 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.
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