## Distinguishing CML from CLL ### Philadelphia Chromosome — The Gold Standard Discriminator **Key Point:** The Philadelphia chromosome t(9;22) resulting in the BCR-ABL1 fusion gene is pathognomonic for CML and is present in >95% of cases. This is the single most reliable feature that separates CML from CLL. ### Comparison Table: CML vs CLL | Feature | CML | CLL | |---------|-----|-----| | **Philadelphia chromosome t(9;22)** | **Present (>95%)** | **Absent** | | Cell lineage | Myeloid | Lymphoid (B-cell) | | Peripheral blood | Myeloid left shift, basophilia, eosinophilia | Mature lymphocytes, smudge cells | | Splenomegaly | Very common (90%) | Common (50–60%) | | Leukocyte count | Often >50,000/μL | Variable, often modest | | Median age at diagnosis | 50–60 years | >70 years | | BCR-ABL1 transcript | BCR-ABL p210 (most common) | Absent | ### Why Philadelphia Chromosome Is Superior 1. **Cytogenetic hallmark:** Present in nearly all CML cases; virtually never in CLL. 2. **Molecular target:** Drives pathogenesis via constitutive tyrosine kinase activity. 3. **Diagnostic criterion:** WHO classification mandates BCR-ABL1 positivity for CML diagnosis. 4. **Therapeutic relevance:** Tyrosine kinase inhibitors (imatinib, dasatinib, nilotinib) are standard of care for CML but not CLL. **Clinical Pearl:** A patient with myeloid leukocytosis and Philadelphia chromosome positivity is CML until proven otherwise. Conversely, a lymphoid leukocytosis with Philadelphia chromosome would be extremely rare and would represent a CML in lymphoid blast crisis or a rare BCR-ABL1+ lymphoma. **High-Yield:** FISH or PCR for BCR-ABL1 is now the standard diagnostic method; karyotyping alone may miss variant translocations. Always order BCR-ABL1 testing in any chronic leukemia with myeloid predominance. [cite:Robbins 10e Ch 13]
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