BCR-ABL is an abnormal fusion gene formed by a translocation between chromosomes 9 and 22, known as the Philadelphia chromosome (Ph+).
- BCR gene: From chromosome 22
- ABL gene: From chromosome 9
This translocation creates a BCR-ABL tyrosine kinase, which is constitutively active, meaning it’s always “on,” leading to:
- Uncontrolled cell proliferation
- Reduced apoptosis (cell death)
- Genomic instability
Clinical Relevance:
- Most commonly associated with:
- Chronic Myeloid Leukemia (CML) (~95% of cases)
- Philadelphia chromosome–positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Pharmacologic Target:
The BCR-ABL fusion protein is a key therapeutic target.
TKIs (Tyrosine Kinase Inhibitors):
These drugs inhibit the BCR-ABL kinase, suppressing leukemic cell growth.
Pharmacist Considerations
- Monitor for resistance mutations (e.g., T315I – resistant to most TKIs except ponatinib).
- Evaluate adherence, as non-adherence can lead to resistance.
- Manage drug interactions, especially with CYP3A4 substrates/inhibitors.
- Be vigilant about side effects: myelosuppression, QT prolongation, hepatotoxicity.