Myeloproliferative Neoplasms (MPNs)

Types of Myeloproliferative Neoplasms

There are several different types of MPNs, classified based on the type of blood cell that is overproduced:

• Chronic Myeloid Leukaemia (CML): Involves overproduction of white blood cells (particularly neutrophils). It is driven by the Philadelphia chromosome, which creates the BCR-ABL fusion gene. Symptoms include fatigue, weight loss, fever, and splenomegaly. Treatment includes targeted therapies such as imatinib.
• Polycythaemia Vera (PV): Characterised by excess red blood cells, leading to thickened blood and increased clot risk. Commonly caused by a JAK2 mutation. Symptoms include headaches, dizziness, itching after warm showers, and increased risk of stroke or heart attack. Treatment includes phlebotomy and medications such as hydroxyurea or JAK2 inhibitors (e.g., ruxolitinib).
• Essential Thrombocythemia (ET): Involves overproduction of platelets, causing abnormal clotting or bleeding. Often linked to JAK2, CALR, or MPL mutations. Treatment includes aspirin and, in some cases, hydroxyurea.
• Primary Myelofibrosis (PMF): Causes scarring (fibrosis) of the bone marrow, leading to anaemia, splenomegaly, and hepatomegaly. Associated with JAK2, CALR, or MPL mutations. Treatment includes JAK2 inhibitors and, in severe cases, stem cell transplantation.

Common Characteristics of MPNs

• Excessive production of one or more types of blood cells
• Presence of genetic mutations, especially in the JAK2 gene
• Increased risk of blood clots, bleeding, myelofibrosis, or progression to acute leukaemia

Symptoms of MPNs

• Fatigue or general weakness
• Abnormal bleeding or easy bruising
• Enlarged spleen or liver
• Headaches, dizziness, or light-headedness
• Night sweats and unintentional weight loss
• Red or purple skin (in polycythaemia vera)
• Itching, especially after warm showers (in polycythaemia vera)

Diagnosis of MPNs

• Blood tests: Abnormal red blood cell, white blood cell, or platelet counts
• Bone marrow biopsy: Evaluates fibrosis or abnormal cell production
• Genetic testing: Detection of JAK2 V617F, CALR, or MPL mutations
• Cytogenetic analysis: Identification of the Philadelphia chromosome in CML

Treatment of MPNs

Treatment varies depending on the type of MPN and symptom severity. Common approaches include:

• Medications: JAK2 inhibitors (e.g., ruxolitinib) for PV and myelofibrosis
• Hydroxyurea: Used in PV and ET to reduce blood cell production
• Aspirin: Low-dose aspirin to reduce clotting risk in ET
• Imatinib: Targeted therapy for CML that blocks the BCR-ABL protein
• Phlebotomy: Regular blood removal in polycythaemia vera
• Stem cell transplant: Considered in severe myelofibrosis or resistant CML
• Supportive care: Blood transfusions, infection management, and symptom relief

Prognosis

• Polycythaemia vera and essential thrombocythemia are often well-managed with treatment
• Chronic myeloid leukaemia has an excellent prognosis with targeted therapy
• Primary myelofibrosis has a variable prognosis, but newer treatments improve quality of life
• Some MPNs may progress to acute leukaemia or bone marrow failure