Concomitant neutrophil JAK2 mutation screening and PRV-1 expression analysis in myeloproliferative disorders and secondary polycythaemia.

Polycythaemia vera (PV) is closely associated with both an acquired activating mutation of the JAK2 tyrosine kinase (JAK2(V617F)) in granulocyte-derived DNA and increased granulocyte polycythaemia rubra vera-1 (PRV-1) expression. In order to explore the correlation between these two biological markers and compare their diagnostic utility, mutation analysis for JAK2(V617F) and quantitative measurement of granulocyte PRV-1 expression were performed on the same study sample from 100 participants: 38 with PV, 22 with essential thrombocythaemia (ET), 10 with agnogenic myeloid metaplasia (AMM), 19 with secondary polycythaemia (SP) and 11 healthy volunteers. The respective overall (homozygous) JAK2(V617F) mutational frequencies were 95% (26%), 55% (0%), 30% (0%), 0% and 0%. The corresponding figures for increased PRV-1 expression were 89%, 18%, 20%, 21% and 9%. In patients with either ET or AMM, the likelihood of detecting JAK2(V617F) was significantly higher in the presence of an increased PRV-1 expression (83% vs. 38%; P = 0.05). Similarly, in patients with PV, homozygous as compared with heterozygous JAK2(V617F) correlated with higher levels of PRV-1 expression (P = 0.11). The present study suggests an allele dose-dependent effect of JAK2(V617F) on granulocyte PRV-1 expression. However, compared with the PRV-1 assay, mutation screening for JAK2(V617F) displayed greater accuracy in distinguishing PV from SP.