Background
Human myeloproliferative disorders (MPDs) are a group of related, clonal haematological diseases, including polycythaemia vera (PV), essential thrombocythaemia (ET) and idiopathic myelofibrosis (IMF). These disorders are characterised by increased numbers of one or more mature blood cell lineage.
Adequately treated MPDs have a relatively good prognosis. However, through the course of the disease, MPDs may transform into one another or into acute myeloid leukaemia (AML), with adverse prognostic implications for the patient. Consequently, a prompt, accurate diagnosis and regular disease monitoring is critical for the appropriate clinical management of these conditions.
Diagnosing MPDs has been historically challenging due to the lack of definitive diagnostic markers. A range of tests, including a bone marrow biopsy, would have been performed. In early 2005, several research groups described a mutation of the JAK2 gene, in a large proportion of patients with MPDs. The JAK2 mutation therefore provides a specific genetic target for diagnostic testing. Genetic testing is now able to provide many patients with a definitive diagnosis, thus avoiding the need to perform further tests or procedures. However, the JAK2 mutation is acquired and therefore, may only be present in a small proportion of the patients’ cells. Consequently, highly sensitive diagnostic techniques are required for its’ detection.
Work Completed (2005-2006)
We have developed a sensitive real-time PCR-based approach for the detection of the JAK2 mutation in patients with MPDs. We carried out a comparison of this assay with two previously published detection methods and determined that it has comparable sensitivity. The real-time PCR method also provides the potential for quantification of the JAK2 mutation, which may have future applications in the monitoring of disease progression or predicting outcome to treatment. This work has been published in the ‘Journal for Molecular Diagnostics’.