From the Research
Yes, JAK2 mutations can cause macrocytosis, which is an increase in the size of red blood cells, as a result of the dysregulated production of blood cells, including red blood cells, due to the constitutive activation of the JAK-STAT signaling pathway. JAK2 mutations are commonly associated with myeloproliferative neoplasms (MPNs) such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis, which affect bone marrow function and blood cell production 1. The JAK2 V617F mutation specifically leads to uncontrolled production of blood cells, including red blood cells, which can alter red blood cell morphology and lead to macrocytosis, with mean corpuscular volume (MCV) values often exceeding 100 fL.
Key Points to Consider
- Patients with JAK2-positive MPNs may present with other hematologic abnormalities as well, including elevated hemoglobin, increased red cell mass, thrombocytosis, and leukocytosis 2.
- If macrocytosis is detected, especially when accompanied by other blood count abnormalities, JAK2 mutation testing may be warranted as part of the diagnostic workup, particularly in patients without other common causes of macrocytosis such as vitamin B12 or folate deficiency 3.
- The presence of JAK2 mutation is expected in polycythemia vera, while approximately 90% of patients with essential thrombocythemia express mutually exclusive JAK2, CALR, or MPL mutations 4.
- The main goal of therapy in both polycythemia vera and essential thrombocythemia is to prevent thrombohemorrhagic complications, and cytoreductive therapy is recommended for high-risk disease 5.
Management and Treatment
- All patients with polycythemia vera require phlebotomy to keep hematocrit below 45% and once-daily or twice-daily aspirin (81 mg), in the absence of contraindications 2.
- Very low-risk essential thrombocythemia might not require therapy, while aspirin therapy is advised for low-risk disease 3.
- First-line drug of choice for cytoreductive therapy, in both essential thrombocythemia and polycythemia vera, is hydroxyurea, and second-line drugs of choice are interferon-α and busulfan 1.
Prognosis and Outcome
- Median survivals are approximately 15 years for polycythemia vera and 18 years for essential thrombocythemia; the corresponding values for patients age 40 or younger were 37 and 35 years, respectively 2.
- Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in polycythemia vera and essential thrombocythemia 3.
- Leukemic transformation rates at 10 years are estimated at <1% for essential thrombocythemia and 3% for polycythemia vera 1.