An Overview of Myeloproliferative Neoplasms (MPNs)

Published by Dr. Kasturi Mandal | Last updated: June 2025

A myeloproliferative neoplasm (MPN) is a group of clonal hematopoietic stem cell disorders characterized by the overproduction of one or more types of blood cells (red cells, white cells, or platelets) in the bone marrow. These disorders are driven by acquired genetic mutations and have overlapping clinical, pathological, and molecular features.

Classification (WHO 2022)

The World Health Organization (WHO) classifies MPNs into the following major subtypes:

  • 1. Chronic myeloid leukemia (CML), BCR::ABL1-positive
  • 2. BCR::ABL1-negative MPNs:
    • Polycythemia vera (PV)
    • Essential thrombocythemia (ET)
    • Primary myelofibrosis (PMF)

Other less common types include Chronic Neutrophilic Leukemia (CNL) and Chronic Eosinophilic Leukemia (CEL).

Molecular Pathogenesis

Key driver mutations lead to cytokine-independent proliferation. The most common mutations are:

GeneMutationFrequency in MPNs
JAK2V617F~95% in PV, ~50–60% in ET/PMF
CALRExon 9 indels~20–25% in ET/PMF (JAK2-negative)
MPLW515L/K mutations~5–10% in ET/PMF

Diagnosis

Diagnosis requires integrating clinical features (e.g., splenomegaly, thrombosis), laboratory findings (e.g., elevated blood counts), a bone marrow biopsy to assess cellularity, and molecular testing for key driver mutations like JAK2, CALR, and MPL.

A laboratory scientist handling test tubes, representing molecular testing for genetic mutations.
Molecular testing for mutations like JAK2 is essential for an accurate MPN diagnosis.

Prognosis & Risk Stratification

Risk is stratified based on age, blood counts, thrombotic history, and mutational profile. Myelofibrosis carries the most significant risk, while PV and ET are generally more indolent but carry risks of thrombosis, bleeding, and progression to acute myeloid leukemia (AML).

Treatment (Evidence-Based)

Treatment is risk-adapted and aims to manage symptoms and prevent complications. Common strategies include:

  • Polycythemia Vera (PV): Phlebotomy (blood removal) and aspirin, with cytoreductive therapy (e.g., hydroxyurea) for high-risk patients.
  • Essential Thrombocythemia (ET): Aspirin, with cytoreductive therapy for high-risk patients.
  • Primary Myelofibrosis (PMF): JAK inhibitors (like ruxolitinib) to manage symptoms, with allogeneic stem cell transplant being the only curative option for eligible patients.

Monitoring & Complications

Patients require regular monitoring of their blood counts and spleen size. The primary complications are thrombotic (blood clots) and hemorrhagic (bleeding) events, as well as the long-term risk of transformation to AML.

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