Discovery of a single mutation responsible for a number of blood disorders

Scientists have discovered a single mutation that is responsible for a number of blood disorders, reporting their findings in this week’s issue of The Lancet.

Myeloproliferative disorders form a range of haematological malignant diseases, with three main members: polycythaemia vera, essential thrombocythaemia, and idiopathic myelofi- brosis. The disorders are characterised by overactive production of blood cells and can lead to thrombosis, haemorrhage or acute myeloid leukaemia. The absence of a definitive diagnostic test and the scarcity of randomised clinical trials make management of these diseases especially challenging.

Tony Green (Cambridge Institute for Medical Research, UK) and colleagues analysed a candidate gene called JAK2 in 140 patients with myeloproliferative disorders from haematological clinics in the UK. They also took control DNA samples from a population of patients with type 1 diabetes. A single point mutation was identified in the JAK2 gene in 71 (97%) of 73 patients with polycythaemia vera, 29 (57%) of 51 with essential thrombocythaemia, and eight (50%) of 16 with idiopathic myelofibrosis. The mutation was not detected in any of the controls.

Distinguishing myeloproliferative disorders from other blood disorders such as thrombocytosis can be difficult; the authors suggest the detection of the JAK2 mutation could become a widely used diagnostic test.

Professor Green concludes: “For more than a quarter of a century, the myeloproliferative disorders have been known to be clonal haematological malignancies, but the identity of underlying target genes has remained elusive. We have shown that a single acquired point mutation in JAK2 is present in virtually all patients with polycythaemia vera and in about half of those with either essential thrombocythaemia or idiopathic myelofibrosis. It is also important to acknowledge the work of several other research groups who have similar data submitted for publication. These exciting results have important implications for the classification, diagnosis, and treatment of the myeloproliferative disorders and provide insight into their pathogenesis.”