Myeloproliferative neoplasms (MPNs) are myeloid neoplasms, clonal diseases of the blood-forming cells that give rise to granulocytes, monocytes, red cells and platelets, in which one or more blood cell lineages are increased in number. They are classified in two ways that are used side by side: by Philadelphia status and by which lineages are increased.
The Philadelphia translocation, or BCR::ABL1, identifies chronic myeloid leukemia (CML) and nothing else in this family. When it is absent, the classical MPNs are mostly driven by JAK2-related mutations, and they fall into essential thrombocythemia (ET, mainly a raised platelet count), primary myelofibrosis (PMF, in which the marrow becomes fibrotic) and polycythemia vera (PV, mainly a raised red cell mass). The rarer chronic neutrophilic leukemia (CNL) and chronic eosinophilic leukemia (CEL) also belong here.
These diseases share one mechanism: a mutated haematopoietic stem cell overproduces mature cells of the myeloid lineages, and the mutation it carries and the burden of the mutated clone shape which disease appears and how it behaves.
Where to start
Classification comes first, because it sets out the two questions that divide the family. The driver mutations come next, because the individual diseases build on the pathway they switch on. The disease notes follow, beginning with the Philadelphia-positive one.
- Classification and the Myeloid Neoplasm Family explains how the myeloid neoplasms are classified, what the triad of lineage, clinical attribute and biologic attribute means, and where the myeloproliferative neoplasms sit in that framework.
- Driver Mutations and Disease Biology explains the JAK2, CALR and MPL driver mutations, the JAK2 V617F mutation and the pathway it switches on, and why the clinical picture follows the burden of the mutated cells.
- Chronic Myeloid Leukemia covers the Philadelphia-positive member of the family: how it presents, how it is diagnosed, the accelerated and blastic phases it can evolve into when untreated, and what tyrosine kinase inhibitors changed.
- Essential Thrombocythemia covers the disorder whose main manifestation is thrombocytosis, from the differential diagnosis of a raised platelet count to the bone marrow morphology and the risk-adapted management.
- Primary Myelofibrosis covers the pre-fibrotic and overt stages of the disease, their presentation, their risk of progression, their survival and their treatment.
- Polycythemia Vera covers the diagnosis of erythrocytosis, the differential of secondary erythrocytosis, the thrombotic and myelofibrotic complications, and the management that follows the hematocrit.