Can a patient with Myelodysplastic Syndrome (MDS) and fibrosis test positive for JAK2 (Janus Kinase 2)?

From the Guidelines

Yes, Myelodysplastic Syndrome (MDS) with fibrosis can be JAK2 positive, as indicated by the presence of the JAK2-V617F mutation in up to 5% of MDS patients and up to 60% of those with myelodysplastic/myeloproliferative neoplasm (MDS/MPN) 1. MDS is a group of bone marrow disorders characterized by ineffective blood cell production, and when it presents with significant bone marrow fibrosis, it can sometimes harbor the JAK2 V617F mutation that is more typically associated with myeloproliferative neoplasms (MPNs). This creates what some specialists refer to as an overlap syndrome with features of both MDS and MPN. Key characteristics of MDS/MPN include:

• Presence of the JAK2-V617F mutation
• Significant bone marrow fibrosis
• Ineffective blood cell production
• Overlap of MDS and MPN features Patients with JAK2-positive MDS with fibrosis may benefit from JAK inhibitor therapy such as ruxolitinib, particularly if they have significant splenomegaly or constitutional symptoms 1. However, treatment decisions should be individualized based on disease characteristics, patient symptoms, and risk stratification. The presence of JAK2 mutation in MDS with fibrosis often indicates a more complex disease biology and may influence prognosis and treatment approach. Regular monitoring of blood counts and spleen size is essential for patients with this condition. Some important considerations for treatment include:
• Dose adjustment of ruxolitinib based on response and tolerability
• Close monitoring of patient symptoms and disease progression
• Individualized treatment approach based on disease characteristics and patient needs

From the Research

Myelodysplastic Syndrome with Fibrosis and JAK2 Positivity

• A case report and literature review published in 2 describes a rare case of myeloid sarcoma in a patient with JAK2-positive myelodysplastic neoplasms with fibrosis.
• The study found that the patient had a JAK2 V617F mutation, which is a common mutation in myeloproliferative neoplasms, but is less frequently found in myelodysplastic syndromes.
• Another study published in 3 found that the JAK2 V617F mutation was present in 8.3% of patients with myelodysplastic syndrome (MDS), suggesting that JAK2 positivity can occur in MDS patients, including those with fibrosis.

JAK2 Mutation in Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes

• A review of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes published in 4 notes that JAK2V617F mutations can occur in these syndromes, particularly in chronic myelomonocytic leukemia (CMML) and MDS/MPN-unclassifiable (MDS/MPN-U).
• The review suggests that JAK2 mutations may be more common in proliferative subtypes of CMML, which could include patients with fibrosis.

JAK2 Inhibitors in Myeloproliferative Neoplasms

• A review of JAK inhibitors in myeloproliferative neoplasms published in 5 discusses the use of JAK inhibitors, such as ruxolitinib and fedratinib, in the treatment of myelofibrosis and other myeloproliferative neoplasms.
• While the review does not specifically address the use of JAK inhibitors in MDS patients with fibrosis, it suggests that JAK inhibitors may be effective in reducing splenomegaly and alleviating disease-related symptoms in patients with myeloproliferative neoplasms, including those with JAK2 mutations.

Primary Myelofibrosis and JAK2 Mutations

• A review of primary myelofibrosis published in 6 notes that JAK2, CALR, or MPL mutations are present in approximately 90% of patients with primary myelofibrosis.
• The review suggests that the presence of a JAK2 mutation is supportive, but not essential, for the diagnosis of primary myelofibrosis, and that other factors, such as bone marrow morphology and clinical features, should also be considered.