Molecular Classification
Tyrosine kinase, Fusion protein, Oncoprotein
Other Names
Philadelphia chromosome, p210 BCR-ABL, p185 BCR-ABL, p230 BCR-ABL
Disease Roles
Chronic myeloid leukemia (CML)Acute lymphoblastic leukemia (ALL)Mixed phenotype acute leukemia (MPAL)

BCR-ABL fusion protein Overview

The BCR-ABL fusion protein is an abnormal, constitutively active tyrosine kinase resulting from a chromosomal translocation (the Philadelphia chromosome). This fusion leads to uncontrolled cell proliferation and is a hallmark of chronic myeloid leukemia (CML) and other leukemias. BCR-ABL is a major therapeutic target, with tyrosine kinase inhibitors (TKIs) designed to specifically inhibit its activity.

Mechanism of Action

Tyrosine kinase inhibitors (TKIs) bind to the ATP-binding site of the BCR-ABL kinase, preventing its activity and downstream signaling.

Biological Functions

Cell proliferation
Inhibition of apoptosis
Signal transduction
Leukemogenesis
Tyrosine kinase activity

Disease Associations

Chronic myeloid leukemia (CML)
Acute lymphoblastic leukemia (ALL)
Mixed phenotype acute leukemia (MPAL)
Acute myeloid leukemia (AML)

Safety Considerations

  • TKI resistance (due to mutations in the ABL kinase domain)
  • Drug-drug interactions
  • Cardiovascular side effects (e.g., QT prolongation)
  • Myelosuppression
  • Pleural effusion
  • Edema

Interacting Drugs

Imatinib
Dasatinib
Nilotinib
Bosutinib
Ponatinib
Asciminib

Associated Biomarkers

Biomarker
BCR-ABL transcript levels (qPCR)
BCR-ABL protein expression
Philadelphia chromosome detection (cytogenetics/FISH)
ABL kinase domain mutations (for TKI resistance)