Examples of Myeloproliferative Diseases
The Philadelphia chromosome-negative classical myeloproliferative neoplasms (MPNs) include three main entities: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), which can present as either prefibrotic or overtly fibrotic disease 1, 2.
The Classical Philadelphia-Negative MPNs
These three disorders represent the core myeloproliferative diseases in modern classification:
Polycythemia Vera (PV)
- Characterized by elevated hemoglobin (>16.5 g/dL in men, >16 g/dL in women) or hematocrit (>49% in men, >48% in women)
- Nearly always associated with JAK2 mutations (either JAK2V617F or JAK2 exon 12 mutations)
- Shows bone marrow hypercellularity with trilineage proliferation 2
Essential Thrombocythemia (ET)
- Defined by sustained platelet count ≥450 × 10⁹/L
- Bone marrow shows megakaryocytic proliferation with large, mature megakaryocytes
- Associated with JAK2, CALR, or MPL mutations 2
Primary Myelofibrosis (PMF)
- Exists in two forms: prefibrotic PMF (pre-PMF) and overtly fibrotic PMF
- Pre-PMF presents with isolated thrombocytosis initially, while overt PMF commonly presents with anemia and splenomegaly at diagnosis
- Characterized by megakaryocyte proliferation with atypia, with or without bone marrow fibrosis depending on stage
- Harbors JAK2, CALR, or MPL mutations 2, 3
Additional MPNs in the WHO Classification
The broader MPN category also includes:
- Chronic myelogenous leukemia (CML) - distinguished by the Philadelphia chromosome/BCR-ABL1 mutation
- Chronic neutrophilic leukemia (CNL)
- Chronic eosinophilic leukemia (CEL)
- Mastocytosis/mast cell disease
- MPN, unclassifiable 1, 4, 5
Key Molecular Features
Approximately 90% of Philadelphia-negative MPN patients harbor one of three driver mutations: JAK2 (most common), CALR, or MPL 6, 7. These mutations are largely mutually exclusive and activate the JAK-STAT signaling pathway, driving the clonal proliferation characteristic of these disorders 8.
Important Clinical Distinction
The 2016 WHO classification formally recognized prefibrotic PMF as a distinct entity separate from overtly fibrotic PMF, which is clinically important because pre-PMF has a better prognosis and different clinical presentation (thrombocytosis vs. anemia) 3. This distinction helps guide risk stratification and treatment decisions.