BCR-ABL1 is a fusion gene that arises from the rearrangement of two separate genes: BCR (breakpoint cluster region) and ABL1 (Abelson proto-oncogene 1). This rearrangement occurs due to a chromosomal translocation, specifically t(9;22)(q34;q11), which produces the Philadelphia chromosome (Ph).
Key Details
1. Structure of BCR-ABL1:
- BCR gene: Located on chromosome 22, it instructs the production of a protein involved in signal transduction and cell growth regulation.
- ABL1 gene: Found on chromosome 9, it encodes a tyrosine kinase that regulates the cell cycle, differentiation, and apoptosis.
- The fusion of these genes creates a hybrid oncogene, BCR-ABL1, which produces a constitutively active tyrosine kinase.
2. Mechanism of Action:
- The BCR-ABL1 protein functions as a continuously active tyrosine kinase.
- This activity results in:
- Unregulated cell proliferation.
- Reduced apoptosis (cell death).
- Increased genetic instability.
- It disrupts normal cellular signaling pathways, making it a key driver of leukemogenesis (the development of leukemia).

3. Clinical Relevance:
- Diseases Associated with BCR-ABL1:
- Chronic Myeloid Leukemia (CML): Present in over 95% of CML cases.
- Acute Lymphoblastic Leukemia (ALL): Detected in approximately 25% of adult ALL cases and 2-4% of pediatric ALL cases.
- Rarely identified in acute myeloid leukemia (AML).
4. Diagnostic Tests for BCR-ABL1 at Jaipur Molecular Lab
- Cytogenetics (Karyotyping): Detects the Philadelphia chromosome.
- Fluorescence In Situ Hybridization (FISH): Visualizes the fusion of BCR and ABL1 at the chromosomal level.
- Quantitative PCR (qPCR): Measures BCR-ABL1 transcript levels, which is essential for diagnosing and monitoring treatment response.
- Next-Generation Sequencing (NGS): Identifies BCR-ABL1 presence and any mutations in the fusion gene.
5. Types of BCR-ABL1 Transcripts:
- The fusion gene generates different transcripts based on the breakpoints in the BCR and ABL1 genes:
- p190 (e1a2): Commonly found in ALL.
- p210 (b2a2 or b3a2): Most frequently associated with CML.
- p230: Rare, linked to chronic neutrophilic leukemia (CNL).
6. Treatment and Therapeutic Targeting:
- The identification of BCR-ABL1 at Jaipur Molecular Lab has led to targeted therapies that revolutionized the treatment of CML and Ph-positive ALL:
- Tyrosine Kinase Inhibitors (TKIs):
- Imatinib (Gleevec): A first-generation TKI that specifically inhibits BCR-ABL1 kinase.
- Dasatinib, Nilotinib: Second-generation TKIs for patients resistant or intolerant to imatinib.
- Ponatinib: A third-generation TKI designed for BCR-ABL1 mutations, including the T315I mutation.
- Allogeneic Stem Cell Transplant: An option for advanced or TKI-resistant cases.
- qPCR Monitoring: Used to assess minimal residual disease (MRD).
- Tyrosine Kinase Inhibitors (TKIs):
Prognostic Implications:
- Good Prognosis: CML patients treated with TKIs often achieve long-term remission.
- Resistance: Mutations in the BCR-ABL1 kinase domain, such as T315I, may cause resistance, requiring alternative treatments like ponatinib.