Bcr-abl fusion

Definition

The bcr-abl fusion is a genetic abnormality resulting from a translocation between chromosomes 9 and 22, which creates a hybrid gene that encodes an active tyrosine kinase involved in cell proliferation and survival. This abnormality is most commonly associated with chronic myeloid leukemia (CML) and plays a crucial role in the development and progression of this cancer.

5 Must Know Facts For Your Next Test

1. The bcr-abl fusion leads to the production of a constitutively active tyrosine kinase, promoting uncontrolled cell division and resistance to apoptosis.
2. Diagnosis of CML often involves detecting the Philadelphia chromosome through techniques like fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR).
3. Patients with the bcr-abl fusion typically respond well to targeted therapies, particularly imatinib, which specifically inhibits the bcr-abl tyrosine kinase.
4. The presence of the bcr-abl fusion is a key factor in determining prognosis and treatment strategies for patients with CML.
5. Not all leukemias are associated with the bcr-abl fusion; however, its discovery has significantly advanced precision oncology by enabling targeted treatments.

Review Questions

• How does the bcr-abl fusion contribute to the pathogenesis of chronic myeloid leukemia?
  • The bcr-abl fusion produces an active tyrosine kinase that stimulates signaling pathways promoting cell proliferation and survival, leading to the overproduction of myeloid cells characteristic of chronic myeloid leukemia. This abnormal signaling cascade overrides normal regulatory mechanisms in hematopoiesis, contributing to both the onset and progression of CML.
• Discuss the impact of tyrosine kinase inhibitors on patients with the bcr-abl fusion and how they represent a shift towards precision oncology.
  • Tyrosine kinase inhibitors (TKIs) like imatinib target the specific activity of the bcr-abl fusion protein, effectively blocking its role in cell proliferation. This targeted approach allows for effective treatment of CML with fewer side effects compared to traditional chemotherapy, showcasing a significant advancement in precision oncology by personalizing treatment based on genetic abnormalities.
• Evaluate the implications of identifying the bcr-abl fusion in leukemic patients on their overall treatment outcomes and disease management strategies.
  • Identifying the bcr-abl fusion in leukemic patients has profound implications for their treatment outcomes, as it directly informs prognosis and guides therapeutic choices. Patients with this genetic abnormality can benefit from targeted therapies that have shown high efficacy and improved survival rates. The ability to tailor treatment strategies based on specific genetic markers exemplifies how advancements in cancer genomics are transforming disease management and fostering better patient outcomes.

Related terms

Chronic Myeloid Leukemia (CML): A type of cancer that affects the blood and bone marrow, characterized by the overproduction of myeloid cells due to the bcr-abl fusion.

Tyrosine Kinase Inhibitors (TKIs): A class of drugs that target and inhibit the activity of tyrosine kinases, including the bcr-abl fusion protein, to treat cancers like CML.

Philadelphia Chromosome: The name given to the abnormal chromosome 22 that results from the bcr-abl fusion; it serves as a key diagnostic marker for CML.