A 58-year-old man with a 3-year history of chronic myeloid leukemia (CML) in chronic phase is on imatinib therapy. Which of the following is NOT a recognized feature of CML?

Question

Accepted Answer

D. Lymphoblastic transformation occurring in the first 6 months of diagnosis without therapy. ## 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]

Answer

A. Marked left shift with myelocytes and metamyelocytes predominating in peripheral blood

Answer

B. Philadelphia chromosome t(9;22) resulting in BCR-ABL1 fusion gene

Answer

C. Basophilia and eosinophilia as part of the leukemic clone

A 58-year-old man with a 3-year history of chronic myeloid leukemia (CML) in chronic phase is on imatinib therapy. Which of the following is NOT a recognized feature of CML?

Explanation

Philadelphia Chromosome and BCR-ABL1 in CML

Peripheral Blood Features of CML

Basophilia and Eosinophilia

Natural History and Transformation Timeline

Why the Distractors Are Correct

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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