This mutation of the exon 14 was the first mutation of the Tyrosine Kinase JAK2 described in myeloproliferative disorders. It is very frequent in Polycythemia Vera (ca. 95%), but can also be found in Essential Thrombocytemia ET (50-70%) and Primary Myelofibrosis PMF (ca 50%). It was soon discovered that the “allelic burden” of the mutation was very variable reflecting that the mutation is either heterozygous or homozygous (most frequently both kinds of clones co-exist), and that not all cells harbour the mutation, even purified myeloid cells. These observations raise two major issues for determining the JAK2V617F status in clinical samples:
- – the limit of detection of the technique used: is it sensitive enough to detect small clones? and its corollary question: what is the limit of clinical significance of very small clones?
To begin to answer these issues, in the past 4 years European Leukemia Net and MPN&MPNr-EuroNet have collaborated to perform extensive studies of the different assays developed to detect and quantify JAK2V617F. Analysis of the data accumulated by these studies have allowed to determining the most appropriate assays for the detection, the quantification and the study of JAK2V617F residual disease, as described in: http://www.nature.com/leu/journal/vaop/ncurrent/pdf/leu2013219a.pdf
- – the acuracy of the quantification.
These questions are the subject of guidelines which are currently being elaborated by our network’s experts and are expected to be posted online very soon.