## Philadelphia Chromosome in CML **Key Point:** The Philadelphia chromosome, resulting from t(9;22) translocation, is present in >95% of CML cases and is pathognomonic for the disease. ### Molecular Mechanism The translocation juxtaposes the ABL gene (chromosome 9) with the BCR gene (chromosome 22), creating the BCR-ABL fusion gene. This produces a constitutively active tyrosine kinase that drives uncontrolled myeloid proliferation. ### Clinical Significance - **Diagnostic criterion:** Present in chronic phase, accelerated phase, and blast crisis - **Prognostic value:** Its presence defines CML; absence suggests atypical CML or other myeloproliferative neoplasm - **Therapeutic target:** Tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) specifically target BCR-ABL **High-Yield:** The Philadelphia chromosome is the FIRST chromosomal abnormality linked to a specific malignancy and revolutionized targeted therapy in oncology. **Clinical Pearl:** Patients with Philadelphia-negative CML have worse prognosis and different treatment response patterns compared to Philadelphia-positive CML.
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