The pathogenesis of essential thrombocythemia

The identification of new mutations continues to further our understanding of the molecular pathogenesis of essential thrombocythemia and related disorders, and offers opportunities for improvements in diagnosis, risk stratification and disease classification.

Molecular lesions in essential thrombocythemia affect two distinct pathways: cytokine signaling and transcriptional regulation. Signaling pathway mutations show a high degree of phenotypic specificity, in contrast to alterations in transcriptional pathways in which the same mutations are seen in diverse myeloid malignancies. Signaling pathway mutations are directly implicated in driving the myeloproliferation which characterizes essential thrombocythemia, whereas the phenotypic consequences of transcriptional pathway mutations are yet to be elucidated. The expanding lexicon of genetic abnormalities has revealed a surprising degree of clonal heterogeneity in essential thrombocythemia, although the clinical significance of this clonal complexity is currently unclear. Potential clinical applications for mutation screening include streamlining of the diagnostic process, improved risk stratification, and molecular distinction of essential thrombocythemia from related disorders such as polycythemia vera and myelofibrosis.

The genetic lexicon of essential thrombocythemia remains incomplete. Given the current acceleration in sequencing technology, further insights into essential thrombocythemia pathogenesis are likely close at hand.