A 55-year-old man has a hemoglobin of 21 g/dL, hematocrit 64 percent, splenomegaly, and plethora. Leukocyte count and platelets are mildly elevated. Serum erythropoietin level is low. Arterial oxygen saturation is 98 percent. What is the most likely underlying genetic finding?

• A BCR-ABL1 fusion transcript
• B Somatic JAK2 V617F mutation ✓
• C CALR exon 9 frameshift mutation
• D EPO receptor germline mutation causing hypersensitivity

Explanation

The combination of true erythrocytosis with normal oxygen saturation, low erythropoietin, and splenomegaly indicates polycythemia vera, a Philadelphia chromosome-negative myeloproliferative neoplasm. More than 95 percent of cases carry the somatic JAK2 V617F gain-of-function mutation, which renders the erythropoietic progenitors EPO independent and suppresses EPO production. Low EPO excludes secondary polycythemia from hypoxia, BCR-ABL1 defines CML, CALR mutations occur mainly in JAK2-unmutated essential thrombocythemia and myelofibrosis, and primary congenital polycythemia shows elevated or normal EPO.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.