## Philadelphia Chromosome and BCR-ABL1 in CML **Key Point:** The Philadelphia chromosome t(9;22) is present in >95% of CML cases and results in the BCR-ABL1 fusion gene, which produces a constitutively active tyrosine kinase driving uncontrolled myeloid proliferation. ## Peripheral Blood Features of CML **High-Yield:** CML is characterized by a **marked left shift** with myelocytes, metamyelocytes, and bands comprising a significant proportion of the white cell differential. This is a hallmark finding. ## Basophilia and Eosinophilia **Clinical Pearl:** Basophilia and eosinophilia are part of the leukemic clone in CML and increase in frequency as the disease progresses toward blast crisis. Their presence is a marker of disease burden and can indicate accelerated phase. ## Natural History and Transformation Timeline **Key Point:** Without treatment, CML progresses through three phases: - **Chronic phase:** 3–5 years (most patients at diagnosis) - **Accelerated phase:** 6–12 months - **Blast crisis (lymphoid or myeloid):** occurs after chronic and accelerated phases The statement that lymphoblastic transformation occurs in the **first 6 months without therapy** is **incorrect**. Blast crisis typically emerges after 3–5 years in the chronic phase, not within 6 months. Early transformation within months would be exceptionally rare and atypical. ## Why the Distractors Are Correct | Feature | Status | Explanation | |---------|--------|-------------| | Philadelphia chromosome t(9;22) | ✓ Correct | Pathognomonic for CML; present in >95% of cases | | Left shift with myelocytes/metamyelocytes | ✓ Correct | Hallmark of CML; reflects uncontrolled myeloid proliferation | | Basophilia and eosinophilia | ✓ Correct | Part of the leukemic clone; increase with disease progression | | Blast crisis in first 6 months | ✗ **INCORRECT** | Blast crisis occurs after years of chronic phase, not months | [cite:Robbins 10e Ch 13]
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