MPN molecular diagnostics

The detection of JAK2 V617F mutations significantly contributes to the diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF).

More than 90% of PV patients have a JAK2 V617F mutation. A small portion that does not have the JAK2 V617F mutation has mutations in JAK2 exon 12.

In ET and PMF, the incidence of JAK2 V617F is around 50%. Other important mutations are found in CALR and MPL. These generally do not occur together and also do not occur together with the JAK2 V617F mutation. The mutations in CALR are found in exon 9 and result in a net +2 bp frameshift. The mutations in MPL are found in codons 505 and 515.

The JAK2 V617F VAF at diagnosis ranges between 1 and 100%. Similar to the JAK2 V617F mutation, the VAF at diagnosis varies greatly for JAK2 exon 12, CALR, and MPL mutations. Therefore, Sanger sequencing is not suitable for detecting mutations with a low VAF.