Myeloproliferative neoplasms
A family of clonal stem-cell disorders in which a driver mutation (most often JAK2 V617F) constitutively activates JAK-STAT signalling, so one or more mature myeloid lineages are overproduced; the classic Philadelphia-negative trio is polycythaemia vera, essential thrombocythaemia and myelofibrosis, which share a mechanism but differ in which cell line dominates.
Definition
Myeloproliferative neoplasms are clonal haematopoietic stem-cell disorders characterised by overproduction of one or more mature myeloid cell lines. The classic Philadelphia-chromosome-negative group comprises polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, driven by JAK2, CALR or MPL mutations; chronic myeloid leukaemia is the Philadelphia-positive member driven by BCR-ABL1.
First principles
One pathway, three phenotypes
The classic myeloproliferative neoplasms are driven by mutations that switch on the JAK-STAT pathway in the haematopoietic stem cell, making myeloid precursors proliferate without their normal growth-factor signal. Because the driver acts on a multipotent stem cell, the disorders overlap, but each has a dominant lineage: red cells in polycythaemia vera, platelets in essential thrombocythaemia, and a fibrotic, failing marrow in myelofibrosis. Chronic myeloid leukaemia is the Philadelphia-positive member driven instead by BCR-ABL1.
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