JAK2 mutations to the fore in hereditary thrombocythemia

Abstract

Acquired mutations of the gene that encodes the intracellular signalling molecule JAK2 are the most frequently observed disease-driving events of the common myeloproliferative neoplasms. A number of germline JAK2 mutations have recently been described in several kindred with the rare disease of hereditary thrombocythemia, also known as familial thrombocythemia or familial thrombocytosis. These inherited mutations are all located within the pseudo-kinase and kinase domains of JAK2 and have been shown to directly contribute to the thrombocythemic phenotype. Molecular characterisation of the resulting, aberrant signalling signatures may provide insights into genotype-phenotype relationships of both hereditary thrombocythemia and the common myeloproliferative neoplasms.