A specific test for polycythemia vera?

Distinguishing between polycythemia vera (PV) and other polycythemic disorders can be very challenging. Although the diagnosis of PV may be straightforward if patients have the classic criteria as defined by the Polycythemia Vera Study Group, often patients present with an incomplete phenotype. Thus, a simple, readily available laboratory test to establish a diagnosis of PV would be highly desirable. In this issue, Klippel and colleagues (page 3569) report the utility of polycythemia rubra vera-1 (PRV-1) mRNA quantification in granulocytes for discrimination of PV from other polycythemias. The authors also report that PRV-1 may be overexpressed in the neutrophils of some patients with thrombocythemia and idiopathic myelofibrosis; it remains to be established if some patients presenting with a thrombocythemia phenotype may in fact be early PV, as reported by Shih et al,¹  and if those with PRV-1-positive idiopathic myelofibrosis have the spent phase of PV. These investigators have previously reported increased PRV-1 mRNA in PV granulocytes but not in their progenitors. The function of PRV-1 in normal hematopoiesis is unclear, as the amount of this protein does not differ between normal and PV cells.

However, quantification of PRV-1 mRNA may be a useful and specific diagnostic marker of PV. In PV, the EEC assay (endogenous erythroid colonies grown in in vitro cultures without erythropoietin) is specific in experienced hands, but it is not easy to standardize; it is labor intensive and requires expensive reagents. Similarly, assays of the clonality of circulating myeloid cells can be performed only in females, and not every female is informative for the X-chromosome-inactivation-based clonality studies. Other newly described PV abnormalities, such as platelet c-Mpl expression, are difficult to perform and available only in specialized laboratories. In contrast, the PRV-1 test is conceptually simple, has minimal inter- and intra-assay variation, and any competent laboratory equipped with the increasingly widely available real-time polymerase chain reaction (PCR) instrument should be able to perform it. However, occasional patients with congenital polycythemia²  and familial thrombocytosis³  were reported to have elevated PRV-1 levels, raising questions about its specificity. Thus, the usefulness and specificity of the PRV-1 test for PV diagnosis remain to be proved in prospective studies. However, due to its simplicity, the PRV-1 assay is attractive and it eventually may become the preferred PV test for all practicing hematologists.