Myeloproliferative neoplasms: overview
- Topic
Marrow stem cells with a stuck-on growth signal make too many mature blood cells. Later the marrow can scar or turn to leukaemia.
What it is
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders driven by constitutively active tyrosine kinase signalling. Unlike MDS, maturation is effective, so blood counts are high. The main entities are chronic myeloid leukaemia (BCR::ABL1), polycythaemia vera, essential thrombocythaemia and primary myelofibrosis (JAK2, CALR or MPL mutations). All tend to colonize spleen and liver (extramedullary haematopoiesis), cause thrombosis or bleeding, burn out into marrow fibrosis (the spent phase) or transform to acute leukaemia.
Step by step
- A stem cell acquires a kinase-activating mutation (BCR::ABL1, JAK2, CALR or MPL).
- Growth factor-independent signalling (JAK–STAT, RAS–MAPK) drives production of mature cells.
- Blood counts rise: granulocytes in CML, red cells in PV, platelets in ET.
- Neoplastic stem cells home to spleen and liver: extramedullary haematopoiesis, splenomegaly.
- Over years, megakaryocyte cytokines (PDGF, TGF-β) scar the marrow (spent phase), or new mutations cause blast transformation.
The four classic myeloproliferative neoplasms
| Neoplasm | Driver | Main blood finding | Marrow | Main complication |
|---|---|---|---|---|
| Chronic myeloid leukaemia | BCR::ABL1, t(9;22) | Neutrophilia with all stages, basophilia | Hypercellular, granulocytes and small megakaryocytes | Blast crisis |
| Polycythaemia vera | JAK2 V617F (exon 12 in a few) | High red cell mass, often also platelets and neutrophils; low EPO | Panmyelosis | Thrombosis, spent phase |
| Essential thrombocythaemia | JAK2, CALR or MPL | High platelet count | Clusters of giant megakaryocytes | Thrombosis, bleeding, erythromelalgia |
| Primary myelofibrosis | JAK2, CALR or MPL | Anaemia, teardrop cells, leukoerythroblastosis | Fibrosis, atypical megakaryocytes, osteosclerosis | Marrow failure, massive spleen, AML |
Markers
- BCR::ABL1
- JAK2 V617F
- CALR
- MPL
- Reticulin stain
Clinical notes
- Unexplained splanchnic vein thrombosis should prompt testing for JAK2 V617F.
- Hyperuricaemia and gout reflect high cell turnover.
- Kinase inhibitors target BCR::ABL1 in CML and JAK2 signalling in myelofibrosis.
Test yourself
Think of the answer, then tap the question to see it.
What separates MPNs from MDS?
In MPNs differentiation is effective and blood counts are high; in MDS it is ineffective and counts are low.
Which mutation is present in nearly all polycythaemia vera?
JAK2 V617F (a few cases have JAK2 exon 12 mutations).
What is the spent phase of an MPN?
Late marrow fibrosis with falling counts and massive extramedullary haematopoiesis in the spleen.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Myeloproliferative Neoplasms Treatment (PDQ®)–Patient Version (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.