Polycythemia Vera: Current Therapeutic Approaches

Abstract

PV is one of the lower-risk subtypes of MPNs [1] that is characterized primarily by clonal erythrocytosis [2]. It has an annual incidence of 0.21-2.27 per 100,000. Median age at diagnosis is estimated at 71 years. A male preponderance is noted. JAK2 V617F is found in >95% of PV patients and JAK2 exon 12 mutations in ~4% [3]. JAK2 exon 12 mutations such as insertions or deletions are relatively specific to JAK2V617F-negative PV and not found in ET and PMF [4]. JAK2 homozygosity is neither necessary nor sufficient for a PV phenotype as indicated by presence of small or undetectable homozygous clones in some PV patients [5]. Heterozygous mutant erythroblasts of PV patients have distinct transcriptional profiles that precede acquisition of homozygosity and reflect differential activation of phosphorylated STAT1, which modulate erythropoiesis [5]. CALR and MPL have distribution frequency of 0 and 0% [6]. Other mutations (e.g., LNK) have been reported [2]. Co-occurrence of CALR mutation exon 9 with JAK2V617F, usually occurs in less than 1% of PV [4].