From the Guidelines
MPL mutations are not a primary concern in the diagnosis and management of polycythemia vera (PV), as they occur in less than 5% of cases, and the focus should be on testing for JAK2 V617F and JAK2 exon 12 mutations. The European LeukemiaNet (ELN) consortium updated their recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) in 2018, which included revised diagnostic criteria for PV, emphasizing the importance of bone marrow examination and the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2, in the diagnosis of myelofibrosis (MF) 1.
Key Points to Consider
- The primary genetic driver of PV is the JAK2 V617F mutation, which is present in approximately 95% of patients 1.
- MPL mutations are more commonly associated with essential thrombocythemia (ET) and primary myelofibrosis (PMF), where they occur in about 3-5% and 5-10% of cases, respectively.
- The rarity of MPL mutations in PV reflects the distinct molecular pathogenesis of this disease compared to other myeloproliferative neoplasms.
- The ELN recommendations suggest that both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea 1.
Clinical Implications
- When evaluating a patient with suspected PV, testing should focus primarily on JAK2 V617F and JAK2 exon 12 mutations rather than MPL mutations.
- The molecular distinction between MPL mutations and JAK2 mutations helps explain the different clinical phenotypes observed across the spectrum of myeloproliferative neoplasms.
- Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score, and in certain situations for those with intermediate-1 risk score 1.
From the Research
MPL Mutations in PV
- There is no direct evidence in the provided studies regarding MPL mutations in Polycythaemia Vera (PV) [ 2, 3, 4, 5, 6 ].
- The studies primarily focus on the treatment of PV, including the use of ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor, and its efficacy and safety in patients with PV [ 2, 4, 5, 6 ].
- Some studies discuss the pathogenesis of PV, including the role of JAK2 mutations, such as JAK2V617F, but do not mention MPL mutations [ 4 ].
- Overall, there is a lack of information on MPL mutations in PV in the provided studies, suggesting that further research may be needed to understand the relationship between MPL mutations and PV [ 2, 3, 4, 5, 6 ].