A 64-year-old man presents with fatigue and splenomegaly. CBC: Hb 10.2 g/dL, WBC 78,000/μL with a left shift (blasts 3%, myelocytes 18%, basophils 8%), platelets 450,000/μL. JAK2 V617F mutation is NEGATIVE. BCR-ABL1 fusion gene by RT-PCR is POSITIVE. The karyotype shows a small marker chromosome at 22. What is the most likely diagnosis?

• A Polycythemia vera
• B Primary myelofibrosis
• C Chronic myelomonocytic leukemia (CMML)
• D Chronic myeloid leukemia (CML) ✓

Explanation

BCR-ABL1 fusion gene from the reciprocal t(9;22) translocation producing the Philadelphia chromosome (the small chromosome 22 = Ph chromosome) is the molecular hallmark of CML. The peripheral blood smear in CML characteristically shows a spectrum of myeloid maturation with basophilia (basophilia >2% is a clue), left shift, and low blast count in chronic phase. JAK2 mutation is characteristic of other myeloproliferative neoplasms (PV, ET, PMF) but is absent in CML. Treatment is imatinib (first-generation TKI) or second-generation TKIs (nilotinib, dasatinib).

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.